Blocking a single brain enzyme helped short-circuit a key hunger signal in mice and made them eat less, lose weight and have better blood sugar control, U.S. researchers said on Tuesday.
While much more research lies ahead, they said the finding may lead to new treatments for obesity and diabetes in humans.
"We believe we have identified an important drug development target that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management," said Tony Means of Duke University Medical Center in Durham, North Carolina, whose study appears in the journal Cell Metabolism.
Dr. Means's team focused on the enzyme CaMKK2, which plays a role in appetite stimulation in mice and in humans. Found in a region of the brain known as the hypothalamus, it takes its orders from a hormone released in the gut known as ghrelin, which is released when the stomach is empty.
Ghrelin is already linked to appetite control.
In a separate brain imaging study in the same journal, researchers at the Neurological Institute at McGill University in Montreal showed that ghrelin not only makes people feel hungry, but it makes food look more appealing by activating pleasure signals in the brain.
Dr. Means's idea is to find a way to interrupt ghrelin's activity by toning down the CaMKK2 enzyme's response to the hunger signal.
His team found that mice genetically engineered to lack the enzyme CaMKK2 stayed slim regardless of whether they were on a low-fat or high-fat diet...
Sunday, September 26, 2010
Virus 'link' to childhood obesity
A virus which causes respiratory infections has been linked to childhood obesity, in a study that is likely to reignite a controversial debate.
Previous animal research has implicated common viruses in weight gain, but the evidence has been disputed.
The latest study, in Pediatrics, found that obese children with antibodies specific to a certain virus weighed 35lbs (15.8kg) more than those without.
Nothing has yet been proven on this theory, say UK experts.
Previous research has shown that chicken or mice injected with similar types of viruses showed a statistically significant weight gain...
Previous animal research has implicated common viruses in weight gain, but the evidence has been disputed.
The latest study, in Pediatrics, found that obese children with antibodies specific to a certain virus weighed 35lbs (15.8kg) more than those without.
Nothing has yet been proven on this theory, say UK experts.
Previous research has shown that chicken or mice injected with similar types of viruses showed a statistically significant weight gain...
Study Clarifies Obesity-Infertility Link
Being obese has long been linked to infertility in females, but researchers may have been wrong about how the link was forged, a new study suggests.
Doctors and scientists have thought that the fertility problems were caused by resistance to the hormone insulin. Chronically high levels of insulin often accompany obesity, eventually making muscles and other tissues impervious to the hormone’s signals.
A new study in mice shows that the pituitary gland, which helps regulate the release of fertility-associated hormones, remains sensitive to insulin. But in obese mice, insulin’s constant signaling to release the fertility hormones leads to an overabundance of those hormones, and consequently infertility, researchers report in the Sept. 8 Cell Metabolism.
The discovery firmly ties metabolism to fertility in an unexpected way and may have implications for treating women with a condition known as polycystic ovary syndrome, which is characterized by abnormal menstrual cycles and is often associated with obesity and type 2 diabetes...
Doctors and scientists have thought that the fertility problems were caused by resistance to the hormone insulin. Chronically high levels of insulin often accompany obesity, eventually making muscles and other tissues impervious to the hormone’s signals.
A new study in mice shows that the pituitary gland, which helps regulate the release of fertility-associated hormones, remains sensitive to insulin. But in obese mice, insulin’s constant signaling to release the fertility hormones leads to an overabundance of those hormones, and consequently infertility, researchers report in the Sept. 8 Cell Metabolism.
The discovery firmly ties metabolism to fertility in an unexpected way and may have implications for treating women with a condition known as polycystic ovary syndrome, which is characterized by abnormal menstrual cycles and is often associated with obesity and type 2 diabetes...
Poor biological clock leads to obesity
UC San Diego biologists have discovered biological clocks of mammals are related to development of obesity and diabetes.
It also raises the possibility that some of the rise in diabetes could be a consequence of disturbances in sleep-wake cycles from our increasingly around-the-clock lifestyles.
"We know that mice that don't have good biological clocks tend to develop diabetes and obesity. And we know that mice that have developed diabetes and obesity tend not to have very good biological clocks," Nature quoted Steve Kay at UC San Diego, as saying.
"But what we found that's so significant is that a particular biological clock protein, cryptochrome, is actually regulating how the hormone that regulates glucose production in the liver works in a very specific way," he added.
The study also indicates why shift workers, whose biological clocks are often out of step, also have a greater risk of developing obesity and insulin resistance...
It also raises the possibility that some of the rise in diabetes could be a consequence of disturbances in sleep-wake cycles from our increasingly around-the-clock lifestyles.
"We know that mice that don't have good biological clocks tend to develop diabetes and obesity. And we know that mice that have developed diabetes and obesity tend not to have very good biological clocks," Nature quoted Steve Kay at UC San Diego, as saying.
"But what we found that's so significant is that a particular biological clock protein, cryptochrome, is actually regulating how the hormone that regulates glucose production in the liver works in a very specific way," he added.
The study also indicates why shift workers, whose biological clocks are often out of step, also have a greater risk of developing obesity and insulin resistance...
U.S. animal study shows vitamin D protects against obesity-induced endometrial cancer
Findings from an animal study suggest that obese women can reduce their increased risk of endometrial disease if they take vitamin D supplements, say researchers at the Georgetown University Lombardi Comprehensive Cancer Center.
The scientists report in Cancer Prevention Research published online Tuesday that 25 percent of obese mice fed a vitamin D supplemented diet developed endometrial cancer, while 67 percent of obese mice not treated with the vitamin developed cancer. They also report that vitamin D offered no protective effects for normal weight mice; whether or not they used the vitamin, about 60 percent of these mice developed cancer.
All of the mice were genetically predisposed to develop endometrial cancer, because they were missing one of their two PTEN tumor suppressor genes, loss of which is strongly linked to development of human endometrial cancer. Obesity is also a strong known risk factor, researchers say.
"Vitamin D has been shown to be helpful in a number of cancers, but for endometrial cancer, our study suggests it protects only against cancer that develops due to obesity," says the study's lead investigator, Leena Hilakivi-Clarke, a professor of Oncology. "Still, if these results are confirmed in women, use of vitamin D may be a wonderfully simple way to reduce endometrial cancer risk...
The scientists report in Cancer Prevention Research published online Tuesday that 25 percent of obese mice fed a vitamin D supplemented diet developed endometrial cancer, while 67 percent of obese mice not treated with the vitamin developed cancer. They also report that vitamin D offered no protective effects for normal weight mice; whether or not they used the vitamin, about 60 percent of these mice developed cancer.
All of the mice were genetically predisposed to develop endometrial cancer, because they were missing one of their two PTEN tumor suppressor genes, loss of which is strongly linked to development of human endometrial cancer. Obesity is also a strong known risk factor, researchers say.
"Vitamin D has been shown to be helpful in a number of cancers, but for endometrial cancer, our study suggests it protects only against cancer that develops due to obesity," says the study's lead investigator, Leena Hilakivi-Clarke, a professor of Oncology. "Still, if these results are confirmed in women, use of vitamin D may be a wonderfully simple way to reduce endometrial cancer risk...
Sunday, September 05, 2010
Reset your body clock? Maybe, new study suggests
Scientists have used experimental drugs being developed by Pfizer to reset and restart the body clock of mice in a lab and say their work may offer clues on a range of human disorders, from jetlag to bipolar disorder.
The drugs, which are not yet available in a form suitable for humans and could take many years to develop into human medicines, work by altering the activity of an enzyme which helps set the speed of the body clock.
Researchers say they could potentially restore rhythms in people whose body clocks are messed up by shift work, or in psychiatric disorders like depression, and may even have implications for metabolic problems such as obesity...
The drugs, which are not yet available in a form suitable for humans and could take many years to develop into human medicines, work by altering the activity of an enzyme which helps set the speed of the body clock.
Researchers say they could potentially restore rhythms in people whose body clocks are messed up by shift work, or in psychiatric disorders like depression, and may even have implications for metabolic problems such as obesity...
'Sprouty' protein could be a therapeutic target for obesity, osteoporosis
A newly discovered protein termed as 'sprouty' protein could be the answer to obesity and/or osteoporosis, as well as diabetes, osteoarthritis and heart disease.
Scientists from Maine report findings on the protein that could regulate body fat and bone mass.
They found that the more of this protein that the transgenic mice expressed, the leaner and stronger they became, and when mice with low levels of the Sprouty protein were made to express more of it, they lost weight and increased bone density.
Results showed that the mice with the deleted Sprouty gene had increased body fat and loss of bone mass similar to osteoporosis as compared to normal mice. Adding more Sprouty protein then reversed bone loss. The group with excess Sprouty expression produced lean mice with increased bone mass...
Scientists from Maine report findings on the protein that could regulate body fat and bone mass.
They found that the more of this protein that the transgenic mice expressed, the leaner and stronger they became, and when mice with low levels of the Sprouty protein were made to express more of it, they lost weight and increased bone density.
Results showed that the mice with the deleted Sprouty gene had increased body fat and loss of bone mass similar to osteoporosis as compared to normal mice. Adding more Sprouty protein then reversed bone loss. The group with excess Sprouty expression produced lean mice with increased bone mass...
Eating at right time a must to keep obesity at bay
Eating less and exercising more to keep obesity at bay might not be enough. Now there is new evidence to show that eating at the right time is also a must for weight loss.
A Northwestern University study has found that eating at irregular times, especially when the body wants to sleep, influences weight gain.
"How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out," said Fred Turek, neurobiology and physiology professor at the Weinberg College of Arts and Sciences and director of the Centre for Sleep and Circadian Biology.
The findings could have implications for developing strategies to combat obesity in humans, as the US and the world battle what has been called an "obesity epidemic". More than 300 million adults worldwide are obese, including more than a third of American adults.
"Their schedules force them to eat at times that conflict with their natural body rhythms. This was one piece of evidence that got us thinking -- eating at the wrong time might be contributing to weight gain," says Arble.
Simply modifying the time of feeding alone can greatly affect body weight, the researchers found, says a university statement.
Mice that were fed a high-fat diet during normal sleeping hours gained significantly more weight (a 48 percent increase) than mice eating the same type and amount of food during naturally wakeful hours (a 20 percent increase).
A Northwestern University study has found that eating at irregular times, especially when the body wants to sleep, influences weight gain.
"How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out," said Fred Turek, neurobiology and physiology professor at the Weinberg College of Arts and Sciences and director of the Centre for Sleep and Circadian Biology.
The findings could have implications for developing strategies to combat obesity in humans, as the US and the world battle what has been called an "obesity epidemic". More than 300 million adults worldwide are obese, including more than a third of American adults.
"Their schedules force them to eat at times that conflict with their natural body rhythms. This was one piece of evidence that got us thinking -- eating at the wrong time might be contributing to weight gain," says Arble.
Simply modifying the time of feeding alone can greatly affect body weight, the researchers found, says a university statement.
Mice that were fed a high-fat diet during normal sleeping hours gained significantly more weight (a 48 percent increase) than mice eating the same type and amount of food during naturally wakeful hours (a 20 percent increase).
Mouse Study May Help Explain Fish Oil's Benefits
Feeding obese mice omega-3 fatty acids reduced inflammation that can lead to diabetes, a new study finds.
Fish oil supplements that contain high levels of omega-3 fatty acids are one of the most popular dietary supplements in the United States. While omega-3 fatty acids are widely believed to be beneficial, exactly how they work hasn't been well understood, said study co-author Saswata Talukdar, a post-doctoral fellow at University of California, San Diego.
By studying fat tissue in the mice consuming fish oil, researchers found omega-3 fatty acids seem to act on a particular receptor on cells, GPR120, which, when activated, blocks inflammatory processes.
Chronic inflammation can lead to insulin resistance, a precursor to diabetes.
Therefore, "if we can fix the inflammation part, it's possible that we could prevent insulin resistance or even ameliorate diabetes," Talukdar explained.
The study was published in the Sept. 3 issue of the journal Cell...
Fish oil supplements that contain high levels of omega-3 fatty acids are one of the most popular dietary supplements in the United States. While omega-3 fatty acids are widely believed to be beneficial, exactly how they work hasn't been well understood, said study co-author Saswata Talukdar, a post-doctoral fellow at University of California, San Diego.
By studying fat tissue in the mice consuming fish oil, researchers found omega-3 fatty acids seem to act on a particular receptor on cells, GPR120, which, when activated, blocks inflammatory processes.
Chronic inflammation can lead to insulin resistance, a precursor to diabetes.
Therefore, "if we can fix the inflammation part, it's possible that we could prevent insulin resistance or even ameliorate diabetes," Talukdar explained.
The study was published in the Sept. 3 issue of the journal Cell...
Born lazy: how genes dictate our love of exercise
Researchers discovered that the love of wanting to keep fit is in your genes and can be passed on from generation to generation.
Conversely, the same is true about being a couch potato.
In the future, people who suffer from laziness could be treated with medicine that targets the genes that specifically promote activity.
Scientists from the University of California found that on laboratory mice activity levels could be enhanced by selective breeding – the process of breeding animals for particular genetic traits.
Their study showed that mice bred to enjoy running produce offspring that also like it, showing that the baby mice had inherited the trait of high activity.
Professor Theodore Garland Jr, a biologist and lead author, said: "Our findings have implications for human health...
Conversely, the same is true about being a couch potato.
In the future, people who suffer from laziness could be treated with medicine that targets the genes that specifically promote activity.
Scientists from the University of California found that on laboratory mice activity levels could be enhanced by selective breeding – the process of breeding animals for particular genetic traits.
Their study showed that mice bred to enjoy running produce offspring that also like it, showing that the baby mice had inherited the trait of high activity.
Professor Theodore Garland Jr, a biologist and lead author, said: "Our findings have implications for human health...
Monday, August 30, 2010
Why men and women gain weight in different areas of the body
Why is it that men and women put on those extra kilos in different areas of the body? The answer may not be far away as researchers are close to revealing vital sex differences in men and women concerning fat storage.
The research has indicated that fat is genetically different in men and women.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," said Deborah Clegg, of the UT Southwestern Medical Center.
"The notion that fat cells between males and females are alike is inconsistent with our findings," he said.
Mice store their fat similar to humans in a sexually dimorphic pattern. Just like human males, male mice store their fat in the belly and midsection area while females store fat in their hips, thighs and buttocks...
The research has indicated that fat is genetically different in men and women.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," said Deborah Clegg, of the UT Southwestern Medical Center.
"The notion that fat cells between males and females are alike is inconsistent with our findings," he said.
Mice store their fat similar to humans in a sexually dimorphic pattern. Just like human males, male mice store their fat in the belly and midsection area while females store fat in their hips, thighs and buttocks...
Exercise 'can control appetite'
Exercise not only burns off calories, it can reduce feelings of hunger, scientists have said.
The findings suggest a "double whammy" benefit that may help the overweight to slim.
Researchers studying obese mice found that exercise restored the sensitivity of brain cells involved in controlling appetite.
The change increased satiety - or "feeling full" - in the animals and led to a reduction in food intake...
The findings suggest a "double whammy" benefit that may help the overweight to slim.
Researchers studying obese mice found that exercise restored the sensitivity of brain cells involved in controlling appetite.
The change increased satiety - or "feeling full" - in the animals and led to a reduction in food intake...
Saturday, August 21, 2010
Novel Diabetes Hope Comes from Chinese Herbs
Emodin, a natural product that can be extracted from various Chinese herbs including Rheum palmatum and Polygonum cuspidatum, shows promise as an agent that could reduce the impact of type 2 diabetes. Findings published in this month's edition of the British Journal of Pharmacology show that giving emodin to mice with diet-induced obesity lowered blood glucose and serum insulin, improved insulin resistance and lead to more healthy levels of lipid in the blood. It also decreased body weight and reduced central fat mass..
Thursday, August 12, 2010
Wouldn’t it be Great if You Could Pop a Pill and Lose Weight?
And wouldn't it be great if that pill weren't something advertised on late-night TV, but rather a legitimate treatment? A drug called rimonabant, introduced in Europe, seemed to fit the bill at first, but it was pulled from the market in late 2008 due to concerns about psychiatric side effects.
The story doesn't end there, though. New research on animals suggests that a second generation of drugs may treat obesity without those side effects. A presentation at the International Congress on Obesity in Stockholm, Sweden, revealed a treatment that has the same weight-loss effect as rimonabant, but without impacting the brain.
What's different? The new drug, currently called TM38837, does not affect peripheral organs and tissues. Rimonabant, however, didn't discriminate. According to earlier research, rimonabant doubled the risk of disorders such as depression and suicide.
In their new work, scientists tried the second-generation drug on mice and rats. After a five-week course of treatment, the mice had lost 22 to 26 percent more weight than mice in a control group. The rats had lost 14 percent more than the controls. In both cases, weight loss from TM38837 was the same as weight loss from rimonabant. Separate studies, including dissections and behavioral tests, showed that the drug was less likely to impact the brains of test animals...
The story doesn't end there, though. New research on animals suggests that a second generation of drugs may treat obesity without those side effects. A presentation at the International Congress on Obesity in Stockholm, Sweden, revealed a treatment that has the same weight-loss effect as rimonabant, but without impacting the brain.
What's different? The new drug, currently called TM38837, does not affect peripheral organs and tissues. Rimonabant, however, didn't discriminate. According to earlier research, rimonabant doubled the risk of disorders such as depression and suicide.
In their new work, scientists tried the second-generation drug on mice and rats. After a five-week course of treatment, the mice had lost 22 to 26 percent more weight than mice in a control group. The rats had lost 14 percent more than the controls. In both cases, weight loss from TM38837 was the same as weight loss from rimonabant. Separate studies, including dissections and behavioral tests, showed that the drug was less likely to impact the brains of test animals...
Sunday, August 08, 2010
Light Shed on Triglyceride Metabolism
New findings reported in the July issue of Cell Metabolism, are offering new leads as to why some people might suffer from high levels of triglycerides. High triglycerides are a risk factor for atherosclerosis and cardiovascular disease. They can also lead to inflammation of the pancreas, the researchers said...
It seems that a protein known as GPIHBP1 is the key. Mice lacking that protein end up with LPL built up outside of their muscle and fat tissue instead of where it belongs in capillaries. They show that GPIHBP1 normally sits on the surface of capillary cells, where it actively transports LPL.
The new findings offer an explanation for what had been a surprising finding; Gpihbp1-deficient mice develop severe hypertriglyceridemia, even when they eat a normal diet of mouse chow. Very recently, other researchers have also shown that some people with elevated triglyceride levels carry mutations in their GPIHBP1 gene...
It seems that a protein known as GPIHBP1 is the key. Mice lacking that protein end up with LPL built up outside of their muscle and fat tissue instead of where it belongs in capillaries. They show that GPIHBP1 normally sits on the surface of capillary cells, where it actively transports LPL.
The new findings offer an explanation for what had been a surprising finding; Gpihbp1-deficient mice develop severe hypertriglyceridemia, even when they eat a normal diet of mouse chow. Very recently, other researchers have also shown that some people with elevated triglyceride levels carry mutations in their GPIHBP1 gene...
Saturday, August 07, 2010
Calling all Obelixes! Hope at home - Indian researchers join global scramble to develop anti-obesity pill
New Delhi, July 31: A team of industry researchers in India has synthesised novel compounds that interfere with weight-gaining mechanisms in the body and joined an international scramble to develop a new class of anti-obesity pills.
The team at Dr Reddy’s Laboratories (DRL), Hyderabad, has shown in laboratory studies that one of these compounds, code-named 22g, helped gluttonous and obese mice lose 8 per cent of their body weight after seven days of oral medication...
The team at Dr Reddy’s Laboratories (DRL), Hyderabad, has shown in laboratory studies that one of these compounds, code-named 22g, helped gluttonous and obese mice lose 8 per cent of their body weight after seven days of oral medication...
ew loci for blood lipids identified; functional role of 1p13 locus detailed
Bethesda, MD and Boston, MA - Two new studies published this week provide further insights into the genetic underpinnings of variations in blood lipid levels [1,2]. In one large-scale genomewide association study (GWAS), researchers identified 95 loci that showed associations with blood lipid levels, while another group performed a detailed functional genomics analysis showing how a locus on chromosome 1p13, previously associated with low LDL-cholesterol levels and MI, regulates LDL-cholesterol levels.
"The two papers are highly complementary," Dr Sekar Kathiresan (Massachusetts General Hospital, Boston), a senior investigator of both studies, told heartwire. "The reason they're so complementary is that the first paper, the GWAS paper, puts down 95 stakes in the sand, while the second paper drills down on one of those stakes. We think the mapping effort, the GWAS paper, is incredibly important simply based on the scale of the effort. It's safe to say it's the largest genetics study done to date, and these 95 loci explain about 25% of the genetic component for lipid levels, which is among the largest proportion of variation evaluated to date."
The two studies are published in the August 5, 2010 issue of Nature...
To show that SORT1 is the causal gene, the researchers manipulated the gene in mice. With small interfering RNA "knockdown" and "viral overexpression" in the mouse liver, the researchers showed that the upregulation of SORT1 led to significantly lower LDL-cholesterol levels, as much as 80% lower, and that silencing SORT1 increased LDL cholesterol approximately 200%.
"Using these experiments in mice, we were able to prove that sortilin is the right gene for the LDL effect at the chromosome 1 locus," Kathiresan told heartwire. "And then, finally, if sortilin is the right gene, how does sortilin lower LDL cholesterol? We showed that the physiologic mechanism is that higher levels of sortilin lead to less secretion of very low-density lipoprotein (vLDL) from the liver, and vLDL is the precursor to LDL. Having less of the precursor around leads to less LDL, and this was the final piece of the puzzle."...
"The two papers are highly complementary," Dr Sekar Kathiresan (Massachusetts General Hospital, Boston), a senior investigator of both studies, told heartwire. "The reason they're so complementary is that the first paper, the GWAS paper, puts down 95 stakes in the sand, while the second paper drills down on one of those stakes. We think the mapping effort, the GWAS paper, is incredibly important simply based on the scale of the effort. It's safe to say it's the largest genetics study done to date, and these 95 loci explain about 25% of the genetic component for lipid levels, which is among the largest proportion of variation evaluated to date."
The two studies are published in the August 5, 2010 issue of Nature...
To show that SORT1 is the causal gene, the researchers manipulated the gene in mice. With small interfering RNA "knockdown" and "viral overexpression" in the mouse liver, the researchers showed that the upregulation of SORT1 led to significantly lower LDL-cholesterol levels, as much as 80% lower, and that silencing SORT1 increased LDL cholesterol approximately 200%.
"Using these experiments in mice, we were able to prove that sortilin is the right gene for the LDL effect at the chromosome 1 locus," Kathiresan told heartwire. "And then, finally, if sortilin is the right gene, how does sortilin lower LDL cholesterol? We showed that the physiologic mechanism is that higher levels of sortilin lead to less secretion of very low-density lipoprotein (vLDL) from the liver, and vLDL is the precursor to LDL. Having less of the precursor around leads to less LDL, and this was the final piece of the puzzle."...
All-Nighters May Increase Fat Levels in Blood
Disruptions to a person's normal sleep cycle, such as pulling several all-nighters, could lead to an increase in harmful triglycerides in the blood, a new study on mice suggests.
Though further studies are needed to firm up whether the same holds for humans, scientists often use these rodents as models for human systems.
The new findings could have implications for understanding the health effects of night shifts, 14-hour work days and transoceanic flights. High levels of triglycerides in the blood are a risk factor for heart disease and obesity – not only in mice, but also potentially in people, the researchers say...
Though further studies are needed to firm up whether the same holds for humans, scientists often use these rodents as models for human systems.
The new findings could have implications for understanding the health effects of night shifts, 14-hour work days and transoceanic flights. High levels of triglycerides in the blood are a risk factor for heart disease and obesity – not only in mice, but also potentially in people, the researchers say...
Insufficient ALA could be linked to obesity trend
A new study suggests that a deficiency in alpha-linoleic acid (omega-3) coupled with a chronic excess of linoleic acid (omega-6) could lead to ‘inherited obesity’.
The study, published in the Journal of Lipid Research, describes an increase in fat mass of mice over several generations when fed an ‘unbalanced Western diet’.
In addition to trans-generational weight gain, the research also observed the onset of metabolic disorders such as insulin resistance, and the expression of the inflammatory genes involved in obesity as generations advanced.
“Collectively, our data show that continuous exposure to a high-fat diet combined with a high LA:LNA [omega-6:omega-3] ratio over generations triggers a discrete and steady increase in inflammatory stimuli, accompanied by enhancement of fat mass” wrote the researchers.
Unbalanced Intake
The beneficial role that polyunsaturated fatty acids can have on health is well established. However when their intake is unbalanced, these essential fatty acids can enhance factors that can induce obesity, and may have serious long-term effects on human health.
During the last forty years Western societies have seen increases in the level of calories ingested, alongside an increase of over 250 percent in levels omega-6 intake and a fall in levels of omega-3 of 40 percent. This change in diet has coincided with a steady rise in obesity levels through the generations.
Over this time the ratio of omega-6 to omega-3 in a typical Western diet has shifted from the recommended 5-to-1, to 15-to-1 in much of Europe, and can be as high as 40-to-1 in the United States.
Alpha-linoleic acid (ALA) omega-3 is an essential fatty acid that the body cannot make, and therefore must be consumed in the diet. Good sources of ALA include: flaxseed, soybeans, walnuts, and olive oil. The U.S Institute of Medicine recommends an ALA intake of 1.6 grams per day for men and 1.1 grams per day for women.
Assessing the consequences
The new research, led by Gérard Ailhaud at the Université de Nice Sophia-Antipolis in France, exposed several generations of mice to a high omega-6 and low omega-3 "Western" diet and assessed the consequences.
The mice were given unrestricted access to food and water (ad libitum conditions) over several generations in order to allow the mice to self-regulate the intake according to biological needs.
“We chose purposely ad libitum conditions to expose both male and female mice across several generations to a Western-like diet” the researchers explain.
Trans-generational inheritance
The results of the study observe that under conditions of genetic stability and with no change to routine, four generations of a ‘Western-like fat diet’ were sufficient to gradually increase fat mass.
“A gradual trans-generational increase in adiposity can occur in mice fed a Western-like fat diet” wrote the researchers.
The study suggests that an unbalanced diet can lead to changes in the expression of genes that control growth and immune functions.
A gene expression analysis of fat tissue over several generations of the mice observed “discrete and steady changes in certain important players, such as colony stimulating factor-3 (CSF3) and Nocturnin.”
The researchers said “Our data show that expression of CSF-3 increased over generations in mice. These results strongly suggest a role for CSF-3 in stimulating growth of adipocyte progenitors.”...
The study, published in the Journal of Lipid Research, describes an increase in fat mass of mice over several generations when fed an ‘unbalanced Western diet’.
In addition to trans-generational weight gain, the research also observed the onset of metabolic disorders such as insulin resistance, and the expression of the inflammatory genes involved in obesity as generations advanced.
“Collectively, our data show that continuous exposure to a high-fat diet combined with a high LA:LNA [omega-6:omega-3] ratio over generations triggers a discrete and steady increase in inflammatory stimuli, accompanied by enhancement of fat mass” wrote the researchers.
Unbalanced Intake
The beneficial role that polyunsaturated fatty acids can have on health is well established. However when their intake is unbalanced, these essential fatty acids can enhance factors that can induce obesity, and may have serious long-term effects on human health.
During the last forty years Western societies have seen increases in the level of calories ingested, alongside an increase of over 250 percent in levels omega-6 intake and a fall in levels of omega-3 of 40 percent. This change in diet has coincided with a steady rise in obesity levels through the generations.
Over this time the ratio of omega-6 to omega-3 in a typical Western diet has shifted from the recommended 5-to-1, to 15-to-1 in much of Europe, and can be as high as 40-to-1 in the United States.
Alpha-linoleic acid (ALA) omega-3 is an essential fatty acid that the body cannot make, and therefore must be consumed in the diet. Good sources of ALA include: flaxseed, soybeans, walnuts, and olive oil. The U.S Institute of Medicine recommends an ALA intake of 1.6 grams per day for men and 1.1 grams per day for women.
Assessing the consequences
The new research, led by Gérard Ailhaud at the Université de Nice Sophia-Antipolis in France, exposed several generations of mice to a high omega-6 and low omega-3 "Western" diet and assessed the consequences.
The mice were given unrestricted access to food and water (ad libitum conditions) over several generations in order to allow the mice to self-regulate the intake according to biological needs.
“We chose purposely ad libitum conditions to expose both male and female mice across several generations to a Western-like diet” the researchers explain.
Trans-generational inheritance
The results of the study observe that under conditions of genetic stability and with no change to routine, four generations of a ‘Western-like fat diet’ were sufficient to gradually increase fat mass.
“A gradual trans-generational increase in adiposity can occur in mice fed a Western-like fat diet” wrote the researchers.
The study suggests that an unbalanced diet can lead to changes in the expression of genes that control growth and immune functions.
A gene expression analysis of fat tissue over several generations of the mice observed “discrete and steady changes in certain important players, such as colony stimulating factor-3 (CSF3) and Nocturnin.”
The researchers said “Our data show that expression of CSF-3 increased over generations in mice. These results strongly suggest a role for CSF-3 in stimulating growth of adipocyte progenitors.”...
Tuesday, July 27, 2010
Meals as Medicine: Anti-Obesity Effects of Soy in Rat Model of Menopause
Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior, finds that a diet rich in soy prevents weight gain in post-menopausal female rats.
Previous research suggests that reduced levels of the hormone estrogen during menopause are responsible for the increased body weight and abdominal fat often experienced by postmenopausal women. However, while estrogen replacement therapies can reduce weight gain, they also have unwelcome side effects, prompting a search for alternative methods of treatment. Soy naturally contains estrogen-like compounds called phytoestrogens, and so dietary soy may provide an alternative to typical estrogen replacement therapies...
Previous research suggests that reduced levels of the hormone estrogen during menopause are responsible for the increased body weight and abdominal fat often experienced by postmenopausal women. However, while estrogen replacement therapies can reduce weight gain, they also have unwelcome side effects, prompting a search for alternative methods of treatment. Soy naturally contains estrogen-like compounds called phytoestrogens, and so dietary soy may provide an alternative to typical estrogen replacement therapies...
Monday, July 26, 2010
New obesity compound shows promise in mice
A compound similar to the once-promising weight loss drug Acomplia helped obese mice lose weight and lower their blood fats and blood sugar without causing psychological side effects, U.S. researchers said on Monday.
Like Acomplia, the drug targets cannabinoid receptors that become active after smoking marijuana, but the team tinkered with the compound to keep it from crossing over into the brain, reducing the risk of depression, anxiety or other neurological problems seen in the original drug.
While obese mice do not lose as much weight on this new compound, it was just as effective as Acomplia in reducing obesity-related metabolic changes, researchers from the National Institutes of Health and Northeastern University reported in the Journal of Clinical Investigation...
Like Acomplia, the drug targets cannabinoid receptors that become active after smoking marijuana, but the team tinkered with the compound to keep it from crossing over into the brain, reducing the risk of depression, anxiety or other neurological problems seen in the original drug.
While obese mice do not lose as much weight on this new compound, it was just as effective as Acomplia in reducing obesity-related metabolic changes, researchers from the National Institutes of Health and Northeastern University reported in the Journal of Clinical Investigation...
Sunday, July 25, 2010
Resveratrol revs up metabolism, promotes weight loss in first ever primate study
Resveratrol is a type of phytonutrient known as a polyphenol. Found in the skin of grapes, wine, grape juice, peanuts, and berries, it has often been hailed as a life-extending natural compound. After all, research in mice and lab rats has indicated it can protect those animals from obesity and diabetes and has anti-cancer, anti-inflammatory and blood-sugar-lowering effects, too. However, rats and mice are rodents -- and their physiology is in many ways different from the primate family that includes apes, monkeys and, most importantly, human beings...
Scientists find unsuspected molecular link between obesity and insulin resistance
A new understanding of insulin resistance and the action of diabetes drugs such as Avandia and Actos could pave the way for improved medications that are more selective and safer, say scientists from Dana-Farber Cancer Institute and The Scripps Research Institute.
Our findings strongly suggest that good and bad effects of these drugs can be separated by designing second-generation drugs that focus on the newly uncovered mechanism, said Bruce Spiegelman, PhD, of Dana-Farber, senior author on a report appearing in the July 22 issue of Nature.
Avandia and Actos, known generically as rosiglitazone and pioglitazone, are widely used to counteract the obesity-related abnormalities in insulin response that lead to diabetes. The drugs act on a master regulatory protein called PPAR-gamma, primarily in fat cells, which governs genes involved in the bodys response to insulin.
Obesity resulting from a high-fat diet alters the function of PPAR-gamma and disrupts the expression of those insulin response genes, including adipsin and adiponectin. Avandia and Actos work by binding to PPAR-gamma and reversing the gene expression changes.
The drugs were believed to work by stimulating or agonizing the PPAR-gamma receptor, causing it to rev up some genes and dampen the activity of others.
In the Nature report, however, the researchers say they have identified an entirely new and surprising mechanism by which PPAR-gamma can control whole-body insulin sensitivity. It is mainly through this mechanism, they found, that the diabetes drugs counteract insulin resistance – not their agonist effect on PPAR-gamma. Moreover, they say, agonism of PPAR-gamma may be largely responsible for the harmful drug side effects.
The newly identified pathway linking obesity and insulin response involves cdk5, a protein kinase, or molecular switch. When cdk5 is activated by the development of obesity in mice, it causes a chemical change in PPAR-gamma called phosphorylation. In contrast to agonism of PPAR-gamma, phosphorylation has a narrow effect, disrupting a smaller set of genes that lead to insulin resistance...
Our findings strongly suggest that good and bad effects of these drugs can be separated by designing second-generation drugs that focus on the newly uncovered mechanism, said Bruce Spiegelman, PhD, of Dana-Farber, senior author on a report appearing in the July 22 issue of Nature.
Avandia and Actos, known generically as rosiglitazone and pioglitazone, are widely used to counteract the obesity-related abnormalities in insulin response that lead to diabetes. The drugs act on a master regulatory protein called PPAR-gamma, primarily in fat cells, which governs genes involved in the bodys response to insulin.
Obesity resulting from a high-fat diet alters the function of PPAR-gamma and disrupts the expression of those insulin response genes, including adipsin and adiponectin. Avandia and Actos work by binding to PPAR-gamma and reversing the gene expression changes.
The drugs were believed to work by stimulating or agonizing the PPAR-gamma receptor, causing it to rev up some genes and dampen the activity of others.
In the Nature report, however, the researchers say they have identified an entirely new and surprising mechanism by which PPAR-gamma can control whole-body insulin sensitivity. It is mainly through this mechanism, they found, that the diabetes drugs counteract insulin resistance – not their agonist effect on PPAR-gamma. Moreover, they say, agonism of PPAR-gamma may be largely responsible for the harmful drug side effects.
The newly identified pathway linking obesity and insulin response involves cdk5, a protein kinase, or molecular switch. When cdk5 is activated by the development of obesity in mice, it causes a chemical change in PPAR-gamma called phosphorylation. In contrast to agonism of PPAR-gamma, phosphorylation has a narrow effect, disrupting a smaller set of genes that lead to insulin resistance...
Lose sleep, get fat?
LOS ANGELES — Disrupted sleep patterns seem to contribute to the risk of obesity and diabetes, according to numerous studies. Researchers have theorized that disrupted circadian rhythms throw off various hormonal processes in the body that contribute to disease.
This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at University of Texas Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.
One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels.
The study shows that disruption of these genes only in the pancreas causes early signs of diabetes...
This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at University of Texas Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.
One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels.
The study shows that disruption of these genes only in the pancreas causes early signs of diabetes...
AMRI Announces Phase I Study of Novel Drug for Obesity Treatment
ALBANY, N.Y., Jul 21, 2010 (BUSINESS WIRE) -- AMRI (AMRI 6.86, +0.34, +5.21%) has commenced enrollment for a Phase I study of ALB-127158(a), a novel MCH1 receptor antagonist offering a potential new approach for the treatment of obesity. The announcement was made yesterday during a presentation by AMRI's Dr. Peter Guzzo, director, discovery research and development, at the 6th Obesity and Diabetes Drug Development Summit in Arlington, VA. Preclinical data were also reported.
The clinical trial will be comprised of a single ascending dose study followed by a multiple ascending dose study to assess safety, tolerability and pharmacokinetics. The multiple ascending dose study will be conducted in overweight subjects to evaluate pharmacodynamics (the physiological effects of the drug candidate on the body), including caloric intake, hunger assessments and metabolic markers. The Phase I study is anticipated to be completed during the first quarter of 2011.
Preclinical studies of the AMRI compound have suggested promise for the treatment of human obesity. For example, in data presented by Dr. Guzzo, ALB-127158(a) showed high levels of MCH1 receptor occupancy leading to a sustained, dose-related reduction in food intake in dietary-induced obese mice. The ensuing weight loss of up to 18% after 28 days of administration was substantially higher than that from the currently available therapeutic agent, sibutramine. Weight loss was shown to be entirely due to a reduction in food intake leading to a preferential reduction in fat stores and was accompanied by significant improvements in glucose tolerance. Preliminary safety evaluation, including cardiovascular safety, was also reported; subsequent regulatory safety testing supported approval by the UK Medicines and Healthcare Products Regulatory Agency for initiation of the Phase I study...
The clinical trial will be comprised of a single ascending dose study followed by a multiple ascending dose study to assess safety, tolerability and pharmacokinetics. The multiple ascending dose study will be conducted in overweight subjects to evaluate pharmacodynamics (the physiological effects of the drug candidate on the body), including caloric intake, hunger assessments and metabolic markers. The Phase I study is anticipated to be completed during the first quarter of 2011.
Preclinical studies of the AMRI compound have suggested promise for the treatment of human obesity. For example, in data presented by Dr. Guzzo, ALB-127158(a) showed high levels of MCH1 receptor occupancy leading to a sustained, dose-related reduction in food intake in dietary-induced obese mice. The ensuing weight loss of up to 18% after 28 days of administration was substantially higher than that from the currently available therapeutic agent, sibutramine. Weight loss was shown to be entirely due to a reduction in food intake leading to a preferential reduction in fat stores and was accompanied by significant improvements in glucose tolerance. Preliminary safety evaluation, including cardiovascular safety, was also reported; subsequent regulatory safety testing supported approval by the UK Medicines and Healthcare Products Regulatory Agency for initiation of the Phase I study...
Good news for Obese people
WASHINGTON: Researchers at Washington University School of Medicine in St Louis have found a way to significantly reduce atherosclerosis in mice without lowering cholesterol levels or eliminating other obesity-related problems.
Atherosclerosis is the process through which fatty substances, such as cholesterol and cellular waste products accumulate in the lining of arteries.
Those buildups, called plaques, reduce blood flow through the artery and can contribute to heart attack, stroke and even gangrene. It is common in individuals with obesity-related problems such as high blood pressure, high cholesterol and diabetes.
In the study, researchers inhibited atherosclerosis in mice by interfering with production of a substance called fatty acid synthase.
This enzyme converts dietary sugars into fatty acids in the liver, where it plays an important role in energy metabolism.
But fatty acids also are involved in atherosclerosis.
"The plaques that clog arteries contain large amounts of fatty acids. We engineered mice that are unable to make fatty acid synthase in one of the major cell types that contribute to plaque formation. On a standard Western diet high in fat, the mice had less atherosclerosis than their normal littermates," said senior investigator Dr. Clay F. Semenkovich.
Animals can't survive without fatty acid synthase, so mice in this study were able to make the substance in most of their tissues.
They couldn't manufacture it, however, in macrophages, a type of white blood cell that surrounds and kills invading microorganisms, removes dead cells from the body and stimulates the action of other immune cells.
These mouse experiments suggest targeting fatty acid synthase in macrophages may provide a potential treatment strategy for humans.
The researchers identified factors in the fatty acid pathway that seem to be capable of preventing plaques from blocking arteries in mice.
He says those substances - LXR-alpha and ABCA1 - eventually may become drug targets.
"It may be possible, for example, to take macrophages out of humans, inhibit fatty acid synthase in those cells, and then infuse the macrophages back into the same personFrom what we've observed in mice, we would hypothesize that approach might prevent or interfere with plaque buildup in people," he said...
Atherosclerosis is the process through which fatty substances, such as cholesterol and cellular waste products accumulate in the lining of arteries.
Those buildups, called plaques, reduce blood flow through the artery and can contribute to heart attack, stroke and even gangrene. It is common in individuals with obesity-related problems such as high blood pressure, high cholesterol and diabetes.
In the study, researchers inhibited atherosclerosis in mice by interfering with production of a substance called fatty acid synthase.
This enzyme converts dietary sugars into fatty acids in the liver, where it plays an important role in energy metabolism.
But fatty acids also are involved in atherosclerosis.
"The plaques that clog arteries contain large amounts of fatty acids. We engineered mice that are unable to make fatty acid synthase in one of the major cell types that contribute to plaque formation. On a standard Western diet high in fat, the mice had less atherosclerosis than their normal littermates," said senior investigator Dr. Clay F. Semenkovich.
Animals can't survive without fatty acid synthase, so mice in this study were able to make the substance in most of their tissues.
They couldn't manufacture it, however, in macrophages, a type of white blood cell that surrounds and kills invading microorganisms, removes dead cells from the body and stimulates the action of other immune cells.
These mouse experiments suggest targeting fatty acid synthase in macrophages may provide a potential treatment strategy for humans.
The researchers identified factors in the fatty acid pathway that seem to be capable of preventing plaques from blocking arteries in mice.
He says those substances - LXR-alpha and ABCA1 - eventually may become drug targets.
"It may be possible, for example, to take macrophages out of humans, inhibit fatty acid synthase in those cells, and then infuse the macrophages back into the same personFrom what we've observed in mice, we would hypothesize that approach might prevent or interfere with plaque buildup in people," he said...
Chokeberry Extract Found to Regulate Weight Gain, Blood Glucose, and Inflammation in Rats
Chokeberry bushes have for centuries been residents of eastern deciduous forests where their bright red and dark purple fruits continue to be favorite snacks of local bird species. Native Americans have also traditionally eaten dried chokeberries and prepared teas from parts of the plant, and several domesticated varieties now grace contemporary lawns and gardens from coast to coast. However, the chokeberry (Aronia) is enjoying a new claim-to-fame as a potentially powerful antioxidant, and can now be found for sale in the dietary supplement and "health food" aisles of your local pharmacies and grocery stores.
What makes the humble chokeberry so healthful? Scientists think the answer lies in their unusually high levels of substances called anthocyanins (from the Greek anthos + kyanos meaning dark blue). There are many different anthocyanins in these colorful berries, but they all function as antioxidants -- originally protecting the chokeberry seed from sunshine-induced oxidative stress. And when we eat them, they also appear to protect our bodies from a variety of damaging situations, including exposure to pollution and metabolically-derived free radicals. Indeed, a growing body of scientific literature has shown promising effects of chokeberry consumption on diseases ranging from cancer to obesity. These health-promoting effects may be due to the potent anti-inflammatory properties of anthocyanins, as uncontrolled inflammation is now universally recognized as a common thread in many of our most prevalent and deadly diseases. In addition, certain anthocyanins -- including those found in chokeberry -- have also been shown to improve blood sugar and the function of insulin.
To better understand how chokeberries influence health, Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD studied what happens when prediabetic rats are fed chokeberry extracts for an extended period of time. The results of their research were presented on April 25 at the Experimental Biology 2010 meeting in Anaheim, CA. This presentation is part of the scientific program of the American Society for Nutrition, home of the world's leading nutrition researchers.
The researchers first made 18 male rats "prediabetic" or insulin insensitive by feeding them a fructose-rich diet for 6 weeks. Then they randomized the animals to continue drinking either pure water or water spiked with low or high levels of chokeberry extract (CellBerry®, Integrity Nutraceuticals International). After drinking this water for 6 weeks, the groups were compared in terms of body weight, body fat, blood glucose regulation, and molecular markers for inflammation.
Qin and Anderson found that at the end of the study the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans. And to add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.
Of course, human studies will be needed before scientists can declare whether we derive the same health benefits from the chokeberry...
What makes the humble chokeberry so healthful? Scientists think the answer lies in their unusually high levels of substances called anthocyanins (from the Greek anthos + kyanos meaning dark blue). There are many different anthocyanins in these colorful berries, but they all function as antioxidants -- originally protecting the chokeberry seed from sunshine-induced oxidative stress. And when we eat them, they also appear to protect our bodies from a variety of damaging situations, including exposure to pollution and metabolically-derived free radicals. Indeed, a growing body of scientific literature has shown promising effects of chokeberry consumption on diseases ranging from cancer to obesity. These health-promoting effects may be due to the potent anti-inflammatory properties of anthocyanins, as uncontrolled inflammation is now universally recognized as a common thread in many of our most prevalent and deadly diseases. In addition, certain anthocyanins -- including those found in chokeberry -- have also been shown to improve blood sugar and the function of insulin.
To better understand how chokeberries influence health, Drs. Bolin Qin and Richard Anderson from the US Department of Agriculture in Beltsville, MD studied what happens when prediabetic rats are fed chokeberry extracts for an extended period of time. The results of their research were presented on April 25 at the Experimental Biology 2010 meeting in Anaheim, CA. This presentation is part of the scientific program of the American Society for Nutrition, home of the world's leading nutrition researchers.
The researchers first made 18 male rats "prediabetic" or insulin insensitive by feeding them a fructose-rich diet for 6 weeks. Then they randomized the animals to continue drinking either pure water or water spiked with low or high levels of chokeberry extract (CellBerry®, Integrity Nutraceuticals International). After drinking this water for 6 weeks, the groups were compared in terms of body weight, body fat, blood glucose regulation, and molecular markers for inflammation.
Qin and Anderson found that at the end of the study the rats consuming the chokeberry-spiked water weighed less than the controls; both levels of chokeberry had the same effect in this regard. Similar beneficial effects of chokeberry consumption were found for body fat (specifically, that of the lower abdominal region). They also discovered that animals that had been drinking chokeberry extract had lower blood glucose and reduced levels of plasma triglycerides, cholesterol, and low-density lipoprotein (LDL) cholesterol when compared to the control animals. These alterations would theoretically lead to lower risk for diabetes and cardiovascular disease in humans. And to add even more evidence for a healthful impact of this super-berry, the researchers documented numerous alterations in expression of genes that would likely lead to reduced chronic inflammation and perhaps even lower cancer risk. For instance, drinking chokeberry extract lowered expression of the gene coding for interleukin-6 (IL-6), a protein that normally triggers inflammation following trauma or infection. Chronic overproduction of IL-6 has been documented in many diseases such as diabetes, arthritis, and atherosclerosis and is thought to be a partial cause of these conditions.
Of course, human studies will be needed before scientists can declare whether we derive the same health benefits from the chokeberry...
Tuesday, July 20, 2010
Study Suggests Brown Adipose Tissue Involved in Increased Energy Expenditure after Capsinoids Ingestion
Ajinomoto Co., Inc. and a group led by professor Masayuki Saito of Tenshi College in Sapporo, Japan have found that a single ingestion of capsinoids, a sweet chili pepper extract, appears to increase energy expenditure, especially in people with a high level of activity in brown adipose tissue. The research results were presented at the XI International Congress on Obesity 2010 (ICO 2010) on July 13 in Stockholm, Sweden.
The finding may have implications for controlling obesity, which is affected by the activation of brown adipose tissue according to recent studies.
Previous research with animals such as mice has shown that brown adipose tissue is involved in the regulation of energy expenditure and changes in body-fat levels. Brown adipose tissue in humans and several types of animals is mainly located around the neck and large blood vessels of the thorax. Fat is broken down in the mitochondria of brown adipose tissue cells to generate body heat. Although brown adipose tissue exists to some degree in human infants, the once-conventional view was that the tissue gradually deteriorates and is barely detectable in adults, with virtually no physiological role. In recent years, however, the group led by professor Saito has used PET imaging1 to confirm that brown adipose tissue is present in adults...
The finding may have implications for controlling obesity, which is affected by the activation of brown adipose tissue according to recent studies.
Previous research with animals such as mice has shown that brown adipose tissue is involved in the regulation of energy expenditure and changes in body-fat levels. Brown adipose tissue in humans and several types of animals is mainly located around the neck and large blood vessels of the thorax. Fat is broken down in the mitochondria of brown adipose tissue cells to generate body heat. Although brown adipose tissue exists to some degree in human infants, the once-conventional view was that the tissue gradually deteriorates and is barely detectable in adults, with virtually no physiological role. In recent years, however, the group led by professor Saito has used PET imaging1 to confirm that brown adipose tissue is present in adults...
Omega imbalance can make obesity 'inheritable': study
Overeating combined with the wrong mix of fats in one's diet can cause obesity to be carried over from one generation to the next, researchers in France reported Friday.
Omega-6 and omega-3, both polyunsaturated fatty acids, are each critical to good health.
But too much of the first and not enough of the second can lead to overweight offspring, the scientists showed in experiments with mice designed to mirror recent shifts in human diet.
Over the last four decades, the ratio of omega-6 to omega-3 in a typical Western diet has shifted from a healthy five-to-one to 15-to-one in much of Europe, and up to 40-to-one in the United States.
In the breast milk of American women, the average ratio has gone from six-to-one to 18-to-one.
Earlier studies have established a link between such imbalances and heart disease.
But "this is the first time that we have shown a trans-generational increase in obesity" linked to omega intake, said Gerard Ailhaud, a biochemist at the University of Nice-Sophia Antipolis and main architect of the study.
"Omega six is like a fat-producing bomb," he told AFP by phone.
Experts differ on whether obesity is more importantly due to the percentage of fat in one's diet or the sheer amount of calories consumed.
The findings, published in the US-based Journal of Lipid Research, add yet another dimension to the debate, and could shed new light on the obesity epidemic that has swept across the globe, mainly in rich nations.
They also suggest that persistence within families of health-threatening weight gain -- while not genetic in origin -- may not be entirely due to environmental factors either.
The link between omega imbalance and obesity "is probably epigenetic," said Ailhaud, referring to the complex process whereby the information in genes is translated into chemical activity.
"The genome and the DNA of the rodents has not been modified, but these factors can influence the way in which certain genes are expressed."
In the experiments, four generations of mice were fed a 35-percent fat diet with the omega imbalance now found in much of the developed world.
The result was progressively fatter mice at birth, generation after generation...
Omega-6 and omega-3, both polyunsaturated fatty acids, are each critical to good health.
But too much of the first and not enough of the second can lead to overweight offspring, the scientists showed in experiments with mice designed to mirror recent shifts in human diet.
Over the last four decades, the ratio of omega-6 to omega-3 in a typical Western diet has shifted from a healthy five-to-one to 15-to-one in much of Europe, and up to 40-to-one in the United States.
In the breast milk of American women, the average ratio has gone from six-to-one to 18-to-one.
Earlier studies have established a link between such imbalances and heart disease.
But "this is the first time that we have shown a trans-generational increase in obesity" linked to omega intake, said Gerard Ailhaud, a biochemist at the University of Nice-Sophia Antipolis and main architect of the study.
"Omega six is like a fat-producing bomb," he told AFP by phone.
Experts differ on whether obesity is more importantly due to the percentage of fat in one's diet or the sheer amount of calories consumed.
The findings, published in the US-based Journal of Lipid Research, add yet another dimension to the debate, and could shed new light on the obesity epidemic that has swept across the globe, mainly in rich nations.
They also suggest that persistence within families of health-threatening weight gain -- while not genetic in origin -- may not be entirely due to environmental factors either.
The link between omega imbalance and obesity "is probably epigenetic," said Ailhaud, referring to the complex process whereby the information in genes is translated into chemical activity.
"The genome and the DNA of the rodents has not been modified, but these factors can influence the way in which certain genes are expressed."
In the experiments, four generations of mice were fed a 35-percent fat diet with the omega imbalance now found in much of the developed world.
The result was progressively fatter mice at birth, generation after generation...
Disrupted sleep patterns could add to risk of obesity, diabetes
Disrupted sleep patterns seem to contribute to the risk of obesity and diabetes, according to numerous studies. Researchers have theorized that disrupted circadian rhythms throw off various hormonal processes in the body that contribute to disease.
This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at UT Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.
One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels...
This theory is looking stronger all the time, and the mounting evidence bolsters the argument that people should care about their sleep habits. Researchers at UT Southwestern Medical Center in Dallas have found that mice with defective copies of two genes involved in circadian rhythms develop abnormalities in their pancreatic cells that eventually cause problems with the release of insulin.
One gene, the CLOCK gene, operates in many parts of the body to control circadian processes. The other gene, BMAL1, works with the CLOCK protein. In the study, scientists engineered some mice to have defective CLOCK genes in the pancreas and some to lack the BMAL1 gene. They found that mice with the mutant CLOCK gene were defective in releasing insulin. These mice were prone to obesity and other health problems related to liver and metabolic function. The mice lacking the BMAL1 gene in their pancreas had normal body weight and normal circadian patterns but had abnormal blood sugar levels...
Thursday, July 15, 2010
Crucial Aspects Of Brain Dopamine Signaling Altered By A High Fat Diet
Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that prolonged exposure to a high fat diet is correlated with changes in the brain chemical dopamine within the striatum, a critical component of the brain's reward system.
The authors measured 'real-time' changes in dopamine levels after rats consumed a high fat diet for either 2 or 6 weeks. Compared to rats consuming a standard low fat diet, high-fat diet rats exhibited reduced dopamine release and also reduced reuptake by "dopamine transporters" within the striatum. Mitchell Roitman from the University of Illinois at Chicago says, "Previous research has demonstrated reduced dopamine transporter numbers in association with obesity and exposure to a high fat diet. Our research shows that these changes lead to major differences in the way dopamine functions in the brain." The results from this study highlight the impact of diet on brain neurochemistry - and in particular on brain systems that regulate motivation and willingness to work for food reward in rats as well as humans...
The authors measured 'real-time' changes in dopamine levels after rats consumed a high fat diet for either 2 or 6 weeks. Compared to rats consuming a standard low fat diet, high-fat diet rats exhibited reduced dopamine release and also reduced reuptake by "dopamine transporters" within the striatum. Mitchell Roitman from the University of Illinois at Chicago says, "Previous research has demonstrated reduced dopamine transporter numbers in association with obesity and exposure to a high fat diet. Our research shows that these changes lead to major differences in the way dopamine functions in the brain." The results from this study highlight the impact of diet on brain neurochemistry - and in particular on brain systems that regulate motivation and willingness to work for food reward in rats as well as humans...
New Research Finds That Chemicals In Soy Reduce Weight Gain In A Rat Model Of Menopause
Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that a diet rich in soy prevents weight gain in post-menopausal female rats...
Adiposity Hormone, Leptin, Regulates Food Intake By Influencing Learning And Memory
New animal research reveals mechanism that links memory and feeding behavior with leptin, a hormone released from fat cells
Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that the hormone leptin reduces food intake, in part, by activating the hippocampus, an area of the brain that controls learning and memory function. Leptin is a hormone released from fat cells that acts on the brain to inhibit feeding.
Researchers from the University of Pennsylvania found that when leptin was delivered directly to the hippocampus in rats, the animals consumed less food and lost body weight. Leptin delivered to this region of the brain also impaired the ability of the animals to learn about the spatial location of food...
Research presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, finds that the hormone leptin reduces food intake, in part, by activating the hippocampus, an area of the brain that controls learning and memory function. Leptin is a hormone released from fat cells that acts on the brain to inhibit feeding.
Researchers from the University of Pennsylvania found that when leptin was delivered directly to the hippocampus in rats, the animals consumed less food and lost body weight. Leptin delivered to this region of the brain also impaired the ability of the animals to learn about the spatial location of food...
Greater Risk For Infant Obesity And Pre-Diabetes When Mothers Consumed A High Fat Diet While Nursing; But Not During Pregnancy
The future health of offspring is more negatively impacted when their mothers consume a high fat diet while nursing compared with high-fat diet consumption during pregnancy, according to animal research at Johns Hopkins University. These new research results were presented at the Annual Meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior.
The researchers used a method called "cross-fostering" to determine whether prenatal or postnatal exposure to maternal high fat diet has a greater influence on the development of obesity and diabetes in the offspring. Rats were fed either a low fat or high fat diet during pregnancy. After birth, pups born to mothers that consumed either diet were fostered over to different mother rats that ate the same or opposite diet during the nursing period. The researchers found that rat pups nursed by mothers consuming a high fat diet gained more body weight and were obese when weaned a few weeks later, even if the pup's biological mother ate a low fat diet during pregnancy. In addition to being obese, pups nursed by foster mothers on a high fat diet displayed impaired glucose tolerance, an early indicator of diabetes...
The researchers used a method called "cross-fostering" to determine whether prenatal or postnatal exposure to maternal high fat diet has a greater influence on the development of obesity and diabetes in the offspring. Rats were fed either a low fat or high fat diet during pregnancy. After birth, pups born to mothers that consumed either diet were fostered over to different mother rats that ate the same or opposite diet during the nursing period. The researchers found that rat pups nursed by mothers consuming a high fat diet gained more body weight and were obese when weaned a few weeks later, even if the pup's biological mother ate a low fat diet during pregnancy. In addition to being obese, pups nursed by foster mothers on a high fat diet displayed impaired glucose tolerance, an early indicator of diabetes...
Wednesday, July 14, 2010
Mice Essentially 'Cured' of Mild Diabetes With Enzyme
Nutrition experts at Oregon State University have essentially "cured" laboratory mice of mild, diet-induced diabetes by stimulating the production of a particular enzyme.
The findings could offer a new approach to diabetes therapy, experts say, especially if a drug could be identified that would do the same thing, which in this case was accomplished with genetic manipulation.
Increased levels of this enzyme, called fatty acid elongase-5, restored normal function to diseased livers in mice, restored normal levels of blood glucose and insulin, and effectively corrected the risk factors incurred with diet-induced diabetes.
"This effect was fairly remarkable and not anticipated," said Donald Jump, a professor of nutrition and exercise sciences at Oregon State, where he is an expert on lipid metabolism and principal investigator with OSU's Linus Pauling Institute.
"It doesn't provide a therapy yet, but could be fairly important if we can find a drug to raise levels of this enzyme," Jump said. "There are already some drugs on the market that do this to a point, and further research in the field would be merited."
The studies were done on a family of enzymes called "fatty acid elongases," which have been known of for decades. Humans get essential fatty acids that they cannot naturally make from certain foods in their diet. These essential fatty acids are converted to longer and more unsaturated fatty acids. The fatty acid end products of these reactions are important for managing metabolism, inflammation, cognitive function, cardiovascular health, reproduction, vision and other metabolic roles.
The enzymes that do this are called fatty acid elongases, and much has been learned in recent years about them. In research on diet-induced obesity and diabetes, OSU studied enzyme conversion pathways, and found that elongase-5 was often impaired in mice with elevated insulin levels and diet-induced obesity.
The scientists used an established system, based on a recombinant adenovirus, to import the gene responsible for production of elongase-5 into the livers of obese, diabetic mice. When this "delivery system" began to function and the mice produced higher levels of the enzyme, their diet-induced liver defects and elevated blood sugar disappeared.
"The use of a genetic delivery system such as this was functional, but it may not be a permanent solution," Jump said. "For human therapy, it would be better to find a drug that could accomplish the same thing, and that may be possible. There are already drugs on the market, such as some fibrate drugs, that induce higher levels of elongase-5 to some extent."
There are also drugs used with diabetic patients that can lower blood sugar levels, Jump said, but some have side effects and undesired complications. The potential for raising levels of elongase-5 would be a new, specific and targeted approach to diabetes therapy, he said. While lowering blood sugar, the elevated levels of elongase-5 also reduced triglycerides in the liver, another desirable goal. Elevated triglycerides are associated with "fatty liver," also known as non-alcoholic fatty liver disease. This can progress to more severe liver diseases such as fibrosis, cirrhosis and cancer.
Further research is needed to define the exact biological mechanisms at work in this process, and determine what the fatty acids do that affects carbohydrate and triglyceride metabolism, he said. It appears that high fat diets suppress elongase-5 activity...
The findings could offer a new approach to diabetes therapy, experts say, especially if a drug could be identified that would do the same thing, which in this case was accomplished with genetic manipulation.
Increased levels of this enzyme, called fatty acid elongase-5, restored normal function to diseased livers in mice, restored normal levels of blood glucose and insulin, and effectively corrected the risk factors incurred with diet-induced diabetes.
"This effect was fairly remarkable and not anticipated," said Donald Jump, a professor of nutrition and exercise sciences at Oregon State, where he is an expert on lipid metabolism and principal investigator with OSU's Linus Pauling Institute.
"It doesn't provide a therapy yet, but could be fairly important if we can find a drug to raise levels of this enzyme," Jump said. "There are already some drugs on the market that do this to a point, and further research in the field would be merited."
The studies were done on a family of enzymes called "fatty acid elongases," which have been known of for decades. Humans get essential fatty acids that they cannot naturally make from certain foods in their diet. These essential fatty acids are converted to longer and more unsaturated fatty acids. The fatty acid end products of these reactions are important for managing metabolism, inflammation, cognitive function, cardiovascular health, reproduction, vision and other metabolic roles.
The enzymes that do this are called fatty acid elongases, and much has been learned in recent years about them. In research on diet-induced obesity and diabetes, OSU studied enzyme conversion pathways, and found that elongase-5 was often impaired in mice with elevated insulin levels and diet-induced obesity.
The scientists used an established system, based on a recombinant adenovirus, to import the gene responsible for production of elongase-5 into the livers of obese, diabetic mice. When this "delivery system" began to function and the mice produced higher levels of the enzyme, their diet-induced liver defects and elevated blood sugar disappeared.
"The use of a genetic delivery system such as this was functional, but it may not be a permanent solution," Jump said. "For human therapy, it would be better to find a drug that could accomplish the same thing, and that may be possible. There are already drugs on the market, such as some fibrate drugs, that induce higher levels of elongase-5 to some extent."
There are also drugs used with diabetic patients that can lower blood sugar levels, Jump said, but some have side effects and undesired complications. The potential for raising levels of elongase-5 would be a new, specific and targeted approach to diabetes therapy, he said. While lowering blood sugar, the elevated levels of elongase-5 also reduced triglycerides in the liver, another desirable goal. Elevated triglycerides are associated with "fatty liver," also known as non-alcoholic fatty liver disease. This can progress to more severe liver diseases such as fibrosis, cirrhosis and cancer.
Further research is needed to define the exact biological mechanisms at work in this process, and determine what the fatty acids do that affects carbohydrate and triglyceride metabolism, he said. It appears that high fat diets suppress elongase-5 activity...
Saturday, July 10, 2010
Don’t Just Blame Calories
The grapefruit diet, the Atkins diet, low-fat diets, low-carb diets, the cabbage-soup diet: they and all the other fad diets make the health establishment roll its collective eyes. The only way to lose weight, says every reputable textbook and medical society, is to burn more calories than you consume. And if you are adding pounds, the reason is, pure and simple, that you are consuming more calories than you expend. Weight gain is a straightforward matter of calories in minus calories out, they maintain.
But while the basic math is right, the meaning of “calories in” isn’t what we’ve been taught, according to a growing pile of studies of chubby mice, obese people, svelte mice, and slim people. The calories that matter are not simply the number printed on grocery items, fast-food menus, and those guilt-inducing signs next to Starbucks’ brownies. The calories that count are those extracted by your digestive enzymes and—as more and more research is showing—the trillions of bacteria in your intestine. People whose gut bacteria are better at digesting fats and carbs than their neighbor’s will absorb all 1,500 calories in a Friendly’s Ultimate Grilled Cheese BurgerMelt, while the neighbor will absorb fewer. So even in people with identical metabolisms, the effects of eating identical foods can be different.
The bacteria-made-me-fat idea has been gathering steam since 2006. In that year, Jeffrey Gordon of Washington University and colleagues reported in a paper in Nature that obese mice and slim mice have different populations of gut bacteria. Crucially, they showed that the bacteria caused obesity, rather than obesity producing a specific mix of bacteria. When the scientists plucked bacteria called Firmicutes from obese mice, then put them in the bacteria-free guts of mice raised in a sterile environment, the latter bulked up within 10 to 14 days—even though they ate less...
But while the basic math is right, the meaning of “calories in” isn’t what we’ve been taught, according to a growing pile of studies of chubby mice, obese people, svelte mice, and slim people. The calories that matter are not simply the number printed on grocery items, fast-food menus, and those guilt-inducing signs next to Starbucks’ brownies. The calories that count are those extracted by your digestive enzymes and—as more and more research is showing—the trillions of bacteria in your intestine. People whose gut bacteria are better at digesting fats and carbs than their neighbor’s will absorb all 1,500 calories in a Friendly’s Ultimate Grilled Cheese BurgerMelt, while the neighbor will absorb fewer. So even in people with identical metabolisms, the effects of eating identical foods can be different.
The bacteria-made-me-fat idea has been gathering steam since 2006. In that year, Jeffrey Gordon of Washington University and colleagues reported in a paper in Nature that obese mice and slim mice have different populations of gut bacteria. Crucially, they showed that the bacteria caused obesity, rather than obesity producing a specific mix of bacteria. When the scientists plucked bacteria called Firmicutes from obese mice, then put them in the bacteria-free guts of mice raised in a sterile environment, the latter bulked up within 10 to 14 days—even though they ate less...
Successful dieting is all in the mind
A protein found in cells throughout the body must exist in a specific set of brain neurons to prevent weight gain after chronic feeding on high-calorie meals, revealed a study by researchers at UT Southwestern Medical Center.
Nicknamed the "longevity" protein because of its apparent role in mediating the effects of dietary restriction on life span, SIRT1 has been studied as a potential target for anti-aging drugs.
Prior research has also shown that this metabolic sensor protein in peripheral tissues plays an important role in regulating metabolism, but its physiological relevance in brain neurons remained unclear.
"This is the first study to show that SIRT1 in hypothalamic neurons, specifically POMC neurons, is required for preventing diet-induced obesity and maintaining normal body weight," said Dr. Roberto Coppari, senior author of the mouse study,
POMC, or pro-opiomelanocortin, neurons are found in the hypothalamus region of the brain and are known to play an important role in suppressing appetite and inducing weight loss. There are about 3,000 POMC neurons in a mouse brain.
The researchers genetically engineered mice to lack SIRT1 only in these specific hypothalamic neurons.
They found that when fed a high-calorie diet, the mice lacking SIRT1 in POMC neurons gained more weight and were generally more susceptible to diet-induced obesity than those with the metabolic sensor protein intact.
The mutant mice also had almost twice as much abdominal fat and more of the hormone leptin than those mice with their SIRT1 intact, despite the fact that all the mice maintained the same food intake and movement levels...
Nicknamed the "longevity" protein because of its apparent role in mediating the effects of dietary restriction on life span, SIRT1 has been studied as a potential target for anti-aging drugs.
Prior research has also shown that this metabolic sensor protein in peripheral tissues plays an important role in regulating metabolism, but its physiological relevance in brain neurons remained unclear.
"This is the first study to show that SIRT1 in hypothalamic neurons, specifically POMC neurons, is required for preventing diet-induced obesity and maintaining normal body weight," said Dr. Roberto Coppari, senior author of the mouse study,
POMC, or pro-opiomelanocortin, neurons are found in the hypothalamus region of the brain and are known to play an important role in suppressing appetite and inducing weight loss. There are about 3,000 POMC neurons in a mouse brain.
The researchers genetically engineered mice to lack SIRT1 only in these specific hypothalamic neurons.
They found that when fed a high-calorie diet, the mice lacking SIRT1 in POMC neurons gained more weight and were generally more susceptible to diet-induced obesity than those with the metabolic sensor protein intact.
The mutant mice also had almost twice as much abdominal fat and more of the hormone leptin than those mice with their SIRT1 intact, despite the fact that all the mice maintained the same food intake and movement levels...
Clues for Burning Fat Without Exercise Found in Mice
A brain enzyme that appears to boost body heat in order to burn off excess calories from a high-fat meal has been identified, but because the research was performed in mice, it might not apply to humans.
Learning more about how this enzyme -- PI3 kinase -- boosts calorie burning without exercise (called a thermogenic response) may lead to new ways to fight obesity, according to the research team at the University of Texas Southwestern Medical Center.
"We found that the mice with reduced PI3 kinase activity in specific neurons in the brain gained weight because they were unable to produce this thermogenic response. These mice were more susceptible to diet-induced obesity," study co-senior author Dr. Joel Elmquist, a professor of internal medicine, psychiatry and pharmacology, said in a university news release.
Because the research was conducted in mice, it's unclear whether the findings apply to humans. One of the tissues that plays a role in thermogenic response is brown adipose tissue, a type of fat that isn't common in adult humans...
Learning more about how this enzyme -- PI3 kinase -- boosts calorie burning without exercise (called a thermogenic response) may lead to new ways to fight obesity, according to the research team at the University of Texas Southwestern Medical Center.
"We found that the mice with reduced PI3 kinase activity in specific neurons in the brain gained weight because they were unable to produce this thermogenic response. These mice were more susceptible to diet-induced obesity," study co-senior author Dr. Joel Elmquist, a professor of internal medicine, psychiatry and pharmacology, said in a university news release.
Because the research was conducted in mice, it's unclear whether the findings apply to humans. One of the tissues that plays a role in thermogenic response is brown adipose tissue, a type of fat that isn't common in adult humans...
Thursday, July 01, 2010
Study on effects of resveratrol on metabolism of microcebus murinus
Resveratrol is a natural substance that is widely studied, for its anti-ageing properties among other things. For the first time, work by a team in the "Mécanismes adaptatifs : des organismes aux communautés" Laboratory (CNRS/Muséum National d'Histoire Naturelle) has revealed that this compound reduces weight gain in lemurs. Such findings provide new information regarding the effects of resveratrol on energy metabolism and the control of body mass in primates. They may give a clearer understanding of the factors that govern obesity in humans. This study is published on 22 June 2010 in /BMC Physiology/.
Resveratrol is a polyphenolic compound that is present in certain fruits, such as grape skins, blackberries and peanuts, etc. This compound has been widely studied, notably regarding its effects on ageing, as it has demonstrated that it can increase longevity in numerous animal models. This natural substance also improves the health and survival of mice fed a hyperlipidic diet, but until now, no studies had been performed on primates in this field...
Resveratrol is a polyphenolic compound that is present in certain fruits, such as grape skins, blackberries and peanuts, etc. This compound has been widely studied, notably regarding its effects on ageing, as it has demonstrated that it can increase longevity in numerous animal models. This natural substance also improves the health and survival of mice fed a hyperlipidic diet, but until now, no studies had been performed on primates in this field...
Coconut Oil Could Reduce The Symptoms Of Type 2 Diabetes
A diet including coconut oil, a medium chain fatty acid (MCFA), helps combat insulin resistance.Insulin resistance is the inability of cells to respond to insulin and take in glucose for energy. The pancreas tries to compensate for insulin resistance by producing even more insulin, but eventually glucose accumulates in the bloodstream. Over time, insulin resistance and obesity can lead to pre-diabetes or full-blown type 2 diabetes.
Dr Nigel Turner and colleagues at the Garvan Institute of Medical Research in Darlinghurst, Australia, compared fat metabolism and insulin resistance in mice and rats fed diets rich in coconut oil (a medium chain fatty acid) or lard (a long chain fatty acid). (The lard-based diet was similar to the diet eaten by people in the Western world.) The findings were published in the journal Diabetes.
MCFAs, like in coconut oil, were found to reduce fat accumulation while maintaining insulin action in muscle and fat tissue. "Dietarysupplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance", said Dr. Turner in the study conclusions...
METABOLIC DISEASE: Childhood obesity: possible new insight from mice
Given the current 'epidemic' of obesity and its related diseases (including type 2 diabetes and heart disease), understanding how food intake, body composition, and energy expenditure are regulated has become a research priority. One soluble molecule found to regulate all these processes, and more, is leptin. Leptin causes many of its effects by acting on nerve cells in different regions of the brain, but exactly what effects each brain region mediates has not been clearly determined. However, Lori Zeltser and Laurence Ring have now generated mice in which leptin signaling is disrupted in only the hypothalamic region of the brain and shown that leptin signals in the hypothalamus are required to prevent the development of obesity up to 8 weeks of age. After 8 weeks of age, leptin signals in regions of the brain other than the hypothalamus were able to control further development of obesity, although they could not reverse obesity established prior to 8 weeks of age. The authors suggest that these data might have implications for combating childhood obesity.
TITLE: Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels
AUTHOR CONTACT:
Lori M. Zeltser
Columbia University, New York, New York, USA.
Phone: 212.851.5314; Fax: 212.851.5306; E-mail: lz146@columbia.edu.
View this article at: http://www.jci.org/articles/view/41985?key=ee928b6505cbee5baee5
Saturday, June 19, 2010
The brain may control cholesterol
Cholesterol levels are controlled by a “hormone in the brain” the Daily Mail has reported.
It says the finding offers hope of new treatments to reduce levels of “the dangerous fat”.
The Mail’s story is based on animal research that appears to indicate that blood cholesterol levels are regulated remotely by the central nervous system. The researchers found that increasing levels of a hormone called ghrelin, which is thought to regulate energy intake, caused mice to develop higher levels of cholesterol. The finding that cholesterol can be regulated by the brain could be the basis for new drug treatments, they suggest.
The findings are interesting, but it is important to stress that there are large differences in the way cholesterol affects mice and humans. This is early research that points the way to further research into ghrelin, although more human studies are needed to draw firm conclusions about the brain regulating human blood cholesterol levels. It’s also important to note that, in humans, cholesterol levels can be controlled by diet, exercise and, where necessary, drug treatment...
It says the finding offers hope of new treatments to reduce levels of “the dangerous fat”.
The Mail’s story is based on animal research that appears to indicate that blood cholesterol levels are regulated remotely by the central nervous system. The researchers found that increasing levels of a hormone called ghrelin, which is thought to regulate energy intake, caused mice to develop higher levels of cholesterol. The finding that cholesterol can be regulated by the brain could be the basis for new drug treatments, they suggest.
The findings are interesting, but it is important to stress that there are large differences in the way cholesterol affects mice and humans. This is early research that points the way to further research into ghrelin, although more human studies are needed to draw firm conclusions about the brain regulating human blood cholesterol levels. It’s also important to note that, in humans, cholesterol levels can be controlled by diet, exercise and, where necessary, drug treatment...
Hormone influences sensitivity to sweetness
Scientists have discovered that a blood sugar-regulating hormone may also alter a person's sensitivity to sweet-tasting foods.
Scientists from University of Maryland School of Medicine found that changing the actions of the hormone glucagon could control how foods taste.
"An interesting possibility resulting from our research is that the development of new food additives could change the way you perceive your food, making it taste more or less sweet," said senior author Steven D. Munger, Ph.D., associate professor of anatomy and neurobiology at the University of Maryland School of Medicine.
"From a food industry perspective, such additives could be used to enhance flavour. From a therapeutic perspective, they could be used to treat patients who under-eat or overeat."
When experimented on mice, the researchers found that blocking glucagon's actions using a specific drug made mice less responsive to a sweet solution they were offered. Thus, the actions of these hormones can be directly manipulated in the mouth.
"That leaves open the possibility that we could also enhance sensitivity to sugars by manipulating glucagon in the other direction. That could open doors for food additives to make what we eat taste sweeter without adding more sugar," says Munger.
"Dr. Munger's findings could have great significance for patients who suffer from diabetes, metabolic disorders or obesity," says E. Albert Reece, M.D., Ph.D., M.B.A., acting president of the University of Maryland, Baltimore and John Z. and Akiko K. Bowers Distinguished Professor and dean, University of Maryland School of Medicine...
Scientists from University of Maryland School of Medicine found that changing the actions of the hormone glucagon could control how foods taste.
"An interesting possibility resulting from our research is that the development of new food additives could change the way you perceive your food, making it taste more or less sweet," said senior author Steven D. Munger, Ph.D., associate professor of anatomy and neurobiology at the University of Maryland School of Medicine.
"From a food industry perspective, such additives could be used to enhance flavour. From a therapeutic perspective, they could be used to treat patients who under-eat or overeat."
When experimented on mice, the researchers found that blocking glucagon's actions using a specific drug made mice less responsive to a sweet solution they were offered. Thus, the actions of these hormones can be directly manipulated in the mouth.
"That leaves open the possibility that we could also enhance sensitivity to sugars by manipulating glucagon in the other direction. That could open doors for food additives to make what we eat taste sweeter without adding more sugar," says Munger.
"Dr. Munger's findings could have great significance for patients who suffer from diabetes, metabolic disorders or obesity," says E. Albert Reece, M.D., Ph.D., M.B.A., acting president of the University of Maryland, Baltimore and John Z. and Akiko K. Bowers Distinguished Professor and dean, University of Maryland School of Medicine...
Black Tea Curbs Weight Gain
GUNMA, Japan—Black tea extract suppressed weight gain and fat levels in a recent mice study (doi:10.1016/j.nut.2010.01.019). The Japanese researchers found that black tea extract prevented diet-induced obesity by inhibiting intestinal lipid absorption. They also suggested that the major active component in the black tea extract was the polyphenols.
Using black tea extract, researchers from the Kirin Beverage Company Ltd., Gunma, Japan, prepared a polymerized polyphenol fraction (BTP), and fed it to Male Wistar rats at a concentration of 500 or 1,000 mg/kg body weight. Researchers then measured their plasma lipid levels. Additionally, female mice were fed either a standard or high-fat diet supplemented with 1-percent or 5-percent black tea extract for eight weeks, and changes in body weight were examined.
Both the BTP and black tea extract inhibited pancreatic lipase activity. The black tea extract suppressed increases in rat plasma triglyceride levels in a dose-dependent manner. Furthermore, administration of the 5 percent black tea extract suppressed increases in body weight (P<0.05), parametrial adipose tissue mass and liver lipid content (reduced to 56.9 percent and 81.7 percent of control mice, respectively, P<0.05) in mice fed a high-fat diet.
Using black tea extract, researchers from the Kirin Beverage Company Ltd., Gunma, Japan, prepared a polymerized polyphenol fraction (BTP), and fed it to Male Wistar rats at a concentration of 500 or 1,000 mg/kg body weight. Researchers then measured their plasma lipid levels. Additionally, female mice were fed either a standard or high-fat diet supplemented with 1-percent or 5-percent black tea extract for eight weeks, and changes in body weight were examined.
Both the BTP and black tea extract inhibited pancreatic lipase activity. The black tea extract suppressed increases in rat plasma triglyceride levels in a dose-dependent manner. Furthermore, administration of the 5 percent black tea extract suppressed increases in body weight (P<0.05), parametrial adipose tissue mass and liver lipid content (reduced to 56.9 percent and 81.7 percent of control mice, respectively, P<0.05) in mice fed a high-fat diet.
Fat chance
Throughout the leaner epochs of human history, when food supplies were unreliable, the species would not have survived without a way to hoard calories for later use. That is, without fat. Once a meal has supplied the body’s immediate energy needs, any unused fuel gets converted into long molecules called triglycerides, which are dispatched to fatty tissue where they wait for a signal that the body needs them.
But in an era of high-calorie smorgasbords and 24/7 convenience, unused energy can just pile on year after year, a major reason why one-third of the U.S. adult population is struggling with obesity. Laws of physics — the ones about conservation of matter and energy — dictate that schemes for burning off all that fat are pretty much limited to two options: Diet to lower the amount of energy consumed, or exercise to increase the amount of energy the body needs...
Other than joining a polar bear club, there’s no obvious way to boost your brown fat activity. In May, in the journal Science, Herzig and his colleagues reported that the enzyme COX-2, which is involved in many body processes, plays a role in turning white fat brown. He and his colleagues described experiments in which they rebooted white fat in mice, turning it brown, after increasing the animals’ exposure to COX-2 and mimicking the physiological changes caused by cold. Even more important, mice with new deposits of brown fat lost weight...
But in an era of high-calorie smorgasbords and 24/7 convenience, unused energy can just pile on year after year, a major reason why one-third of the U.S. adult population is struggling with obesity. Laws of physics — the ones about conservation of matter and energy — dictate that schemes for burning off all that fat are pretty much limited to two options: Diet to lower the amount of energy consumed, or exercise to increase the amount of energy the body needs...
Other than joining a polar bear club, there’s no obvious way to boost your brown fat activity. In May, in the journal Science, Herzig and his colleagues reported that the enzyme COX-2, which is involved in many body processes, plays a role in turning white fat brown. He and his colleagues described experiments in which they rebooted white fat in mice, turning it brown, after increasing the animals’ exposure to COX-2 and mimicking the physiological changes caused by cold. Even more important, mice with new deposits of brown fat lost weight...
Scientists identify link between obesity, salt-sensitivity, BP
Medical College of Georgia researchers documented a chain of events in which excess inflammatory factors resulting from excess fat cause the body to retain more sodium and, consequently, more fluid and higher blood pressure.
Dr. Yanbin Dong, geneticist and cardiologist at MCG's Georgia Prevention Institute found that a biomarker in the urine could help identify the most effective therapy for these patients. Dong's team outlined the process that appears to start with fat producing more inflammatory factors, such as interleukin-6, or IL-6.
IL-6 in mice increased production of prostasin, and when it cut fellow protein ENaC it increased its activity and so salt reabsorption. ENaC determines how much sodium to excrete.
Dong said, "It's very special; there are not too many proteases like that. We found that in cells fed IL-6, ENaC gets activated and the cells take in more sodium. It is the last step of your salt reabsorption."...
Dr. Yanbin Dong, geneticist and cardiologist at MCG's Georgia Prevention Institute found that a biomarker in the urine could help identify the most effective therapy for these patients. Dong's team outlined the process that appears to start with fat producing more inflammatory factors, such as interleukin-6, or IL-6.
IL-6 in mice increased production of prostasin, and when it cut fellow protein ENaC it increased its activity and so salt reabsorption. ENaC determines how much sodium to excrete.
Dong said, "It's very special; there are not too many proteases like that. We found that in cells fed IL-6, ENaC gets activated and the cells take in more sodium. It is the last step of your salt reabsorption."...
Protein involved in metabolic dysfunction in obesity identified
A study by Boston University School of Medicine (BUSM) has shown that secreted frizzled-related protein 5 (Sfrp5) is an anti-inflammatory adipokine whose expression is disrupted in animal models of obesity and type 2 diabetes . The research, published in Science, could be key to the development of new approaches to obesity and other metabolic diseases.
Obesity can contribute to metabolic disorders such as type 2 diabetes, which is often associated with a low-grade inflammatory state in adipose tissue . Since adipokine dysregulation is associated with the pathogenesis of obesity-linked disorders, the research team attempted to identify new adipokines by comparing the genetic profile of adipose tissue taken from both lean mice obese mice on a high calorie diet .
Kenneth Walsh, lead author of the study, commented that "Our study shows that Sfrp5 is secreted by adipocytes and that it controls the microenvironment of white adipose tissue under conditions of obesity-induced metabolic stress ...
Obesity can contribute to metabolic disorders such as type 2 diabetes, which is often associated with a low-grade inflammatory state in adipose tissue . Since adipokine dysregulation is associated with the pathogenesis of obesity-linked disorders, the research team attempted to identify new adipokines by comparing the genetic profile of adipose tissue taken from both lean mice obese mice on a high calorie diet .
Kenneth Walsh, lead author of the study, commented that "Our study shows that Sfrp5 is secreted by adipocytes and that it controls the microenvironment of white adipose tissue under conditions of obesity-induced metabolic stress ...
Sunday, June 13, 2010
Mice explain why people are overweight
TOPIC: GENES OF OBESITY: MEDICINE’S NEXT BIG THING?
REPORT: MB #3149
BACKGROUND: Some doctors call obesity the most prevalent, fatal, chronic, and relapsing disorder of the 21st century. It is a leading cause of mortality, morbidity, disability, health care utilization and costs in the U.S. Experts predict the increase in obesity will strain our health care system with millions of additional cases of diabetes, heart disease and disability. Obesity is a disease that impacts more than one-third of the adult American population, which is about 72 million people. More than 66 percent of adult Americans are categorized as being overweight or obese. Since 1960, Americans have increased average heights by 1 inch and average weight by 25 pounds. In 1963, a 10-year-old boy weighed about 74 pounds. Now, the average boy weighs 85 pounds, according to The Obesity Society. Each year, obesity causes about 112,000 excess deaths in America. Obesity is linked to many adverse health effects including high cholesterol, diabetes, hypertension, gallstones, fatty liver disease, sleep apnea, heart failure, birth defects, miscarriages and asthma. Health care costs of American adults with obesity amount to about $147 billion.
GENETIC LINK: The best success stories providing evidence for obesity genes come from several cases of extreme obesity due to mutations of single genes, according to the Centers for Disease Control. Melanocortin 4-receptor gene, which is related to the control of feeding behavior, has been found to be strongly associated with a minority of obesity cases in several populations. Progress in identifying the multiple genes associated with the most common form of obesity has been slow but is accelerating. Single mutations in 11 genes were strongly implicated in 176 cases of obesity worldwide, according to the CDC. Additionally, 50 chromosomal locations relevant to obesity have been mapped with potential causal genes identified in most of those regions...
REPORT: MB #3149
BACKGROUND: Some doctors call obesity the most prevalent, fatal, chronic, and relapsing disorder of the 21st century. It is a leading cause of mortality, morbidity, disability, health care utilization and costs in the U.S. Experts predict the increase in obesity will strain our health care system with millions of additional cases of diabetes, heart disease and disability. Obesity is a disease that impacts more than one-third of the adult American population, which is about 72 million people. More than 66 percent of adult Americans are categorized as being overweight or obese. Since 1960, Americans have increased average heights by 1 inch and average weight by 25 pounds. In 1963, a 10-year-old boy weighed about 74 pounds. Now, the average boy weighs 85 pounds, according to The Obesity Society. Each year, obesity causes about 112,000 excess deaths in America. Obesity is linked to many adverse health effects including high cholesterol, diabetes, hypertension, gallstones, fatty liver disease, sleep apnea, heart failure, birth defects, miscarriages and asthma. Health care costs of American adults with obesity amount to about $147 billion.
GENETIC LINK: The best success stories providing evidence for obesity genes come from several cases of extreme obesity due to mutations of single genes, according to the Centers for Disease Control. Melanocortin 4-receptor gene, which is related to the control of feeding behavior, has been found to be strongly associated with a minority of obesity cases in several populations. Progress in identifying the multiple genes associated with the most common form of obesity has been slow but is accelerating. Single mutations in 11 genes were strongly implicated in 176 cases of obesity worldwide, according to the CDC. Additionally, 50 chromosomal locations relevant to obesity have been mapped with potential causal genes identified in most of those regions...
Research team finds fat-melting protein, development of weight-loss drug likely
A research team has found a microphage-derived protein is capable of breaking down fat masses, which it hopes will lead to the development of a weight-loss drug.
The research team, led by University of Tokyo professor Toru Miyazaki, discovered the macrophage-derived protein, AIM, in 1999. In a bid to examine how the protein functions, they engineered a mouse not to produce AIM and found it grew fatter than ordinary mice eating the same amounts of food.
Researchers then injected AIM into fat cells in the engineered mouse, and confirmed that its fat masses were reduced in size by three-fourths in 72 hours...
The research team, led by University of Tokyo professor Toru Miyazaki, discovered the macrophage-derived protein, AIM, in 1999. In a bid to examine how the protein functions, they engineered a mouse not to produce AIM and found it grew fatter than ordinary mice eating the same amounts of food.
Researchers then injected AIM into fat cells in the engineered mouse, and confirmed that its fat masses were reduced in size by three-fourths in 72 hours...
Tuesday, June 08, 2010
The brain may control cholesterol
Cholesterol levels are controlled by a “hormone in the brain” the Daily Mail has reported. It says the finding offers hope of new treatments to reduce levels of “the dangerous fat”.
The Mail’s story is based on animal research that appears to indicate that blood cholesterol levels are regulated remotely by the central nervous system. The researchers found that increasing levels of a hormone called ghrelin, which is thought to regulate energy intake, caused mice to develop higher levels of cholesterol. The finding that cholesterol can be regulated by the brain could be the basis for new drug treatments, they suggest.
The findings are interesting, but it is important to stress that there are large differences in the way cholesterol affects mice and humans. This is early research that points the way to further research into ghrelin, although more human studies are needed to draw firm conclusions about the brain regulating human blood cholesterol levels. It’s also important to note that, in humans, cholesterol levels can be controlled by diet, exercise and, where necessary, drug treatment..
The researchers found that giving the mice the hormone ghrelin for one week not only caused the expected increase in body fat, but also significantly increased total blood cholesterol levels, compared with a control group. Levels of blood glucose and fats called triglycerides remained unchanged.
They also found that when they genetically deleted or blocked the melanocortin receptor (MC4R) in the central nervous system of the mice, it produced increased levels of 'good' HDL cholesterol. They thought part of the reason for this might be that the neural circuit reduces the uptake of cholesterol by the liver...
The Mail’s story is based on animal research that appears to indicate that blood cholesterol levels are regulated remotely by the central nervous system. The researchers found that increasing levels of a hormone called ghrelin, which is thought to regulate energy intake, caused mice to develop higher levels of cholesterol. The finding that cholesterol can be regulated by the brain could be the basis for new drug treatments, they suggest.
The findings are interesting, but it is important to stress that there are large differences in the way cholesterol affects mice and humans. This is early research that points the way to further research into ghrelin, although more human studies are needed to draw firm conclusions about the brain regulating human blood cholesterol levels. It’s also important to note that, in humans, cholesterol levels can be controlled by diet, exercise and, where necessary, drug treatment..
The researchers found that giving the mice the hormone ghrelin for one week not only caused the expected increase in body fat, but also significantly increased total blood cholesterol levels, compared with a control group. Levels of blood glucose and fats called triglycerides remained unchanged.
They also found that when they genetically deleted or blocked the melanocortin receptor (MC4R) in the central nervous system of the mice, it produced increased levels of 'good' HDL cholesterol. They thought part of the reason for this might be that the neural circuit reduces the uptake of cholesterol by the liver...
Genes and obesity
Thick or thin. Whichever you are, it may not be your fault.
HealthFirst reporter Leslie Toldo says our weight may boil down to a genetic link we share with mice.
Over half of us humans are overweight. That's not really new, but for some, that extra fat may have more to do with destiny than lifestyle.
Lisa Bohner has one wish. "To have life again. To be normal."
She and her 455 pounds struggle every step, every day. "Right now ... I only merely exist."
But this nearly quarter-ton woman may share a genetic link with a one-ounce mouse.
"It's a way that we can illustrate using mouse models with specific genetic characteristics to dissect these processes that are so common in the human population," Dr. Philip Wood, DVM, PhD, said.
Wood created six mouse models in his lab, then inactivated fat-burning genes in each one. Some got fat. Others built up insulin resistance. Others stayed healthy.
Now, he's matching each mouse with a two-footed counterpart -- a person with the same genetic makeup. "We can sort of find the tipping point, if you will. When does obesity show up? When does diabetes show up? When does high blood pressure show up?"
The goal is to indentify people whose genes predispose them to being fat and all the diseases that follow, and find therapies to turn off those switches...
HealthFirst reporter Leslie Toldo says our weight may boil down to a genetic link we share with mice.
Over half of us humans are overweight. That's not really new, but for some, that extra fat may have more to do with destiny than lifestyle.
Lisa Bohner has one wish. "To have life again. To be normal."
She and her 455 pounds struggle every step, every day. "Right now ... I only merely exist."
But this nearly quarter-ton woman may share a genetic link with a one-ounce mouse.
"It's a way that we can illustrate using mouse models with specific genetic characteristics to dissect these processes that are so common in the human population," Dr. Philip Wood, DVM, PhD, said.
Wood created six mouse models in his lab, then inactivated fat-burning genes in each one. Some got fat. Others built up insulin resistance. Others stayed healthy.
Now, he's matching each mouse with a two-footed counterpart -- a person with the same genetic makeup. "We can sort of find the tipping point, if you will. When does obesity show up? When does diabetes show up? When does high blood pressure show up?"
The goal is to indentify people whose genes predispose them to being fat and all the diseases that follow, and find therapies to turn off those switches...
Saturday, May 29, 2010
13 Things You Never Knew About Your Weight
Our team pored over the latest studies, interviewed the top clinicians in obesity science, and listened to the real-life experiences of men and women struggling to maintain their weight. Here, the latest (and often unexpected) thinking behind size and thighs, fatness and fitness...
1. It Really Is Genetic
When scientists first discovered it in certain chubby mice, they called it simply the fatso gene. Years later, when they scoured the human genome for markers that increased vulnerability to type 2 diabetes, the fatso gene (now more politely called FTO) showed up there too. Turns out, people with two copies of the gene were 40 percent more likely to have diabetes and 60 percent more likely to be obese than those without it. Those with only one copy of the gene weighed more too.
Scientists now suspect that there are lots of fat genes.
1. It Really Is Genetic
When scientists first discovered it in certain chubby mice, they called it simply the fatso gene. Years later, when they scoured the human genome for markers that increased vulnerability to type 2 diabetes, the fatso gene (now more politely called FTO) showed up there too. Turns out, people with two copies of the gene were 40 percent more likely to have diabetes and 60 percent more likely to be obese than those without it. Those with only one copy of the gene weighed more too.
Scientists now suspect that there are lots of fat genes.
$10M Awarded To Einstein For Diabetes Research
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) has awarded Albert Einstein College of Medicine of Yeshiva University a five-year, $9.5 million grant for the continuation of its Diabetes Research and Training Center (DRTC). The DRTC was also awarded a $632,000 supplemental grant for equipment and additional pilot and feasibility studies through the American Recovery and Reinvestment Act (ARRA), bringing total NIH support to $10,177,000...
"The ultimate goal of these studies is to develop new therapies for the prevention or treatment of diabetes," said Dr. Pessin. "For example, we recently mapped a signaling pathway that controls energy expenditure in mice. By blocking this pathway, we can increase energy expenditure and cause weight loss in these animals. We're now trying to develop drugs that can interfere with this pathway in humans. If we're successful, we'll take our findings to clinical trials."...
"The ultimate goal of these studies is to develop new therapies for the prevention or treatment of diabetes," said Dr. Pessin. "For example, we recently mapped a signaling pathway that controls energy expenditure in mice. By blocking this pathway, we can increase energy expenditure and cause weight loss in these animals. We're now trying to develop drugs that can interfere with this pathway in humans. If we're successful, we'll take our findings to clinical trials."...
Saturday, May 22, 2010
Sleep apnea ups insulin resistance
The intermittent hypoxia associated with sleep apnea causes a distinct drop in insulin sensitivity in mice, even though chronic hypoxia, such as that associated with high altitude, did not.
The research will be reported at the ATS 2010 International Conference in New Orleans.
To determine whether intermittent hypoxia (IH) and chronic hypoxia (CH) would have different metabolic effects, Dr. Lee and colleagues fitted adult male mice with arterial and venous catheters for continuous rapid blood monitoring of glucose and insulin sensitivity.
They then exposed the mice to either seven hours of IH, in which treatment, oxygen levels oscillated, reaching a low of about 5 percent once a minute, or CH, in which they were exposed to oxygen at a constant rate of 10 percent, and compared each treatment group to protocol-matched controls.
When compared to the control group, the IH mice demonstrated impaired glucose tolerance and reduced insulin sensitivity; the CH group, however, showed only a reduction in glucose tolerance but not insulin sensitivity compared to controls. "Both intermittent hypoxia and continuous hypoxia exposed mice exhibited impaired glucose tolerance, but only the intermittent hypoxia exposed animals demonstrated a reduction in insulin sensitivity," said Euhan John Lee, M.D., a fellow at the Medical Center.
"The intermittent hypoxia of sleep apnea and the continuous hypoxia of altitude are conditions of hypoxic stress that are known to modulate glucose and insulin homeostasis. Although both forms of hypoxia worsen glucose tolerance, this research demonstrated that the increase in insulin resistance that accompanies intermittent hypoxia, or sleep apnea, is greater than that seen with continuous hypoxia, or altitude," explained Dr. Lee.
The specific finding that intermittent, but not continuous, hypoxia induced insulin resistance was not expected.
Increased generation of reactive oxygen species, initiation of pro-inflammatory pathways, elevated sympathetic activity, or upregulation of insulin counter-regulatory hormones in IH may contribute to the greater development of insulin resistance in those mice versus those exposed to continuous hypoxia.
"As sleep apnea continues to rise with the rate of obesity, it will be increasingly important to understand both the independent and interactive effects of both morbidities on the development of metabolic disorders...
The research will be reported at the ATS 2010 International Conference in New Orleans.
To determine whether intermittent hypoxia (IH) and chronic hypoxia (CH) would have different metabolic effects, Dr. Lee and colleagues fitted adult male mice with arterial and venous catheters for continuous rapid blood monitoring of glucose and insulin sensitivity.
They then exposed the mice to either seven hours of IH, in which treatment, oxygen levels oscillated, reaching a low of about 5 percent once a minute, or CH, in which they were exposed to oxygen at a constant rate of 10 percent, and compared each treatment group to protocol-matched controls.
When compared to the control group, the IH mice demonstrated impaired glucose tolerance and reduced insulin sensitivity; the CH group, however, showed only a reduction in glucose tolerance but not insulin sensitivity compared to controls. "Both intermittent hypoxia and continuous hypoxia exposed mice exhibited impaired glucose tolerance, but only the intermittent hypoxia exposed animals demonstrated a reduction in insulin sensitivity," said Euhan John Lee, M.D., a fellow at the Medical Center.
"The intermittent hypoxia of sleep apnea and the continuous hypoxia of altitude are conditions of hypoxic stress that are known to modulate glucose and insulin homeostasis. Although both forms of hypoxia worsen glucose tolerance, this research demonstrated that the increase in insulin resistance that accompanies intermittent hypoxia, or sleep apnea, is greater than that seen with continuous hypoxia, or altitude," explained Dr. Lee.
The specific finding that intermittent, but not continuous, hypoxia induced insulin resistance was not expected.
Increased generation of reactive oxygen species, initiation of pro-inflammatory pathways, elevated sympathetic activity, or upregulation of insulin counter-regulatory hormones in IH may contribute to the greater development of insulin resistance in those mice versus those exposed to continuous hypoxia.
"As sleep apnea continues to rise with the rate of obesity, it will be increasingly important to understand both the independent and interactive effects of both morbidities on the development of metabolic disorders...
Scientists Hope to Trigger Fat-Burning Cells
Last spring, researchers confirmed that brown fat-the kind that burns energy rather than storing it and is especially prevalent in newborns-can be found in small pockets in adults, too, and slimmer adults have more of it. This spring, a team says it might have found one of the first steps in activating that fat-burning fat in adults. Their study comes out in Science this week.
Brown fat is packed with energy-producing mitochondria, and babies have a lot of it because it helps them keep warm. Once humans begin to regulate their own body temperature they don’t need as much brown fat anymore, so it gets replaced by energy-storing white fat, which helps store energy but leads to expanded waistlines in this age of affluence.
Testing on mice, the team led by Stephan Herzig upped the use of an enzyme called cyclooxygenase-2 (COX-2). While the enzyme plays a role in many physiological functions, the researchers found that pushing it in mice could induce their white fat to act more like energy-burning brown fat, and their weight dropped by around 20 percent.
"There has been a lot of excitement around brown fat, but … there wasn’t any clear indication that turning up brown fat would make animals lose weight," says Chad Cowan, a professor in the Department of Stem Cell and Regenerative Biology at Harvard Medical School who studies fat cell development. "What this paper does is make a good link to something that might be clinically beneficial."
Don’t get too excited just yet. This is a test on mice, not people, and there’s another problem: This transformation in the animals, white fat acting like brown fat, happened only when Herzig and his colleagues tricked the mice’s bodies into thinking they were at a colder temperature than they actually were: That caveat is important because the COX-2 enzyme is present in a wide range of body tissues, and revving up its activity may lead to some serious side effects such as clotting problems, increased sensitivity to pain and even muscle abnormalities. Herzig found that manipulating the COX-2 pathway switched white fat to brown fat in the mice only when he simulated cold temperatures through metabolic tweaks - dilating small blood vessels and increasing the pumping of the heart - and made the rodents act as if they were shivering...
Brown fat is packed with energy-producing mitochondria, and babies have a lot of it because it helps them keep warm. Once humans begin to regulate their own body temperature they don’t need as much brown fat anymore, so it gets replaced by energy-storing white fat, which helps store energy but leads to expanded waistlines in this age of affluence.
Testing on mice, the team led by Stephan Herzig upped the use of an enzyme called cyclooxygenase-2 (COX-2). While the enzyme plays a role in many physiological functions, the researchers found that pushing it in mice could induce their white fat to act more like energy-burning brown fat, and their weight dropped by around 20 percent.
"There has been a lot of excitement around brown fat, but … there wasn’t any clear indication that turning up brown fat would make animals lose weight," says Chad Cowan, a professor in the Department of Stem Cell and Regenerative Biology at Harvard Medical School who studies fat cell development. "What this paper does is make a good link to something that might be clinically beneficial."
Don’t get too excited just yet. This is a test on mice, not people, and there’s another problem: This transformation in the animals, white fat acting like brown fat, happened only when Herzig and his colleagues tricked the mice’s bodies into thinking they were at a colder temperature than they actually were: That caveat is important because the COX-2 enzyme is present in a wide range of body tissues, and revving up its activity may lead to some serious side effects such as clotting problems, increased sensitivity to pain and even muscle abnormalities. Herzig found that manipulating the COX-2 pathway switched white fat to brown fat in the mice only when he simulated cold temperatures through metabolic tweaks - dilating small blood vessels and increasing the pumping of the heart - and made the rodents act as if they were shivering...
Researcher Calls Out Laboratory ‘Flab Rats’
A medical researcher is calling out laboratory “flab rats” for their obesity and lack of exercise — and he’s not talking about unfit grad students existing on vending-machine candy . He really means the rats (and mice) themselves, the condition of which he says may be leading “to spurious experimental results.”
Writing in New Scientist, Mark Mattson, chief of the laboratory of neurosciences at the U.S. National Institute on Aging Intramural Research Program, argues that rodents used in experiments are overfed and under-exercised, resulting in health problems that may make them poor research subjects. High blood sugar, high blood pressure, cholesterol problems and obesity, among other ailments, all make them more susceptible to certain diseases and may skew results.
How bad is it? “Some strains of lab rat attain a body weight in excess of 1 kilogram, nearly double that of a healthy rat,” he writes. (We think we’ve actually seen one of those on the NYC subway tracks.)
Here’s what Mattson has to say about implications for cancer research:
We know that some carcinogens are more potent in overweight animals and that couch-potato rodents have an elevated risk of developing tumors. In addition, many types of tumor grow more rapidly in animals with unlimited access to food, and certain aspects of metastasis — the process by which tumors spread to new sites in the body — appear to differ between obese and slender mice. Experimental cancer drugs might therefore act differently in couch-potato individuals than in their slender counterparts.
The researcher writes that animal models for neurodegenerative diseases, cardiovascular diseases and renal problems may also be inaccurate if the animals are fat and out of shape. To better mimic the effects of potential treatments in humans who exercise and are at a healthy weight, he suggests withholding food and providing exercise wheels to some of the rodents being used in experiments...
Writing in New Scientist, Mark Mattson, chief of the laboratory of neurosciences at the U.S. National Institute on Aging Intramural Research Program, argues that rodents used in experiments are overfed and under-exercised, resulting in health problems that may make them poor research subjects. High blood sugar, high blood pressure, cholesterol problems and obesity, among other ailments, all make them more susceptible to certain diseases and may skew results.
How bad is it? “Some strains of lab rat attain a body weight in excess of 1 kilogram, nearly double that of a healthy rat,” he writes. (We think we’ve actually seen one of those on the NYC subway tracks.)
Here’s what Mattson has to say about implications for cancer research:
We know that some carcinogens are more potent in overweight animals and that couch-potato rodents have an elevated risk of developing tumors. In addition, many types of tumor grow more rapidly in animals with unlimited access to food, and certain aspects of metastasis — the process by which tumors spread to new sites in the body — appear to differ between obese and slender mice. Experimental cancer drugs might therefore act differently in couch-potato individuals than in their slender counterparts.
The researcher writes that animal models for neurodegenerative diseases, cardiovascular diseases and renal problems may also be inaccurate if the animals are fat and out of shape. To better mimic the effects of potential treatments in humans who exercise and are at a healthy weight, he suggests withholding food and providing exercise wheels to some of the rodents being used in experiments...
Male, female fat cells different in mice
Genes dictate if fat is stored on belly or hips -- in particular, gender genes, U.S. researchers said.
Researchers at the University of Texas Southwestern Medical Center in Dallas, who studied mice say they were surprised to find major differences between male and female fat cells.
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," senior author Dr. Deborah Clegg said in a statement. "This was completely unexpected. We expected the exact opposite -- that 138 would be different and the rest would be the same between the sexes."
The study, published in the International Journal of Obesity, also found male mice on a high-fat diet gained more weight and had more highly inflamed fat tissue -- especially belly fat -- than female mice eating the same diet.
However, in the female mice whose ovaries had been removed -- a condition similar to human menopause -- put on the high fat diet, weight gain was greater and more likely to be in the belly...
Researchers at the University of Texas Southwestern Medical Center in Dallas, who studied mice say they were surprised to find major differences between male and female fat cells.
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," senior author Dr. Deborah Clegg said in a statement. "This was completely unexpected. We expected the exact opposite -- that 138 would be different and the rest would be the same between the sexes."
The study, published in the International Journal of Obesity, also found male mice on a high-fat diet gained more weight and had more highly inflamed fat tissue -- especially belly fat -- than female mice eating the same diet.
However, in the female mice whose ovaries had been removed -- a condition similar to human menopause -- put on the high fat diet, weight gain was greater and more likely to be in the belly...
Anti-obesity effect of an isoflavone fatty acid ester on obese mice induced by high fat diet and its potential mechanism
The novel compound 1a is one of the isoflavone fatty acid esters. In order to investigate the anti-obesity effect of compound 1a and its potential mechanism of influence in adipocyte differentiation, Obese male C57BL/6J mice induced by high-fat diet (HFD) and rat preadipocytes3T3-L1 cellwere used.MethodAfter 4-week HFD induction, the obese model was made successfully...
Conclusion: Compound 1a regulates serum lipid profiles, decreases adipose tissue mass and body weight gain by inducing adipocyte apoptosis in high fat diet induced mice.
Thus, it may be used to treat obese patients with hypercholesterolemia and hypertriglyceridemia.
Conclusion: Compound 1a regulates serum lipid profiles, decreases adipose tissue mass and body weight gain by inducing adipocyte apoptosis in high fat diet induced mice.
Thus, it may be used to treat obese patients with hypercholesterolemia and hypertriglyceridemia.
Sunday, May 16, 2010
Belly Fat or Hip Fat: It Really Is All in Your Genes, Says Researcher
The age-old question of why men store fat in their bellies and women store it in their hips may have finally been answered: Genetically speaking, the fat tissue is almost completely different.
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," said Dr. Deborah Clegg, assistant professor of internal medicine at UT Southwestern Medical Center and senior author of the study appearing in the International Journal of Obesity. "This was completely unexpected. We expected the exact opposite -- that 138 would be different and the rest would be the same between the sexes."
The study involved mice, which distribute their fat in a sexually dimorphic pattern similar to humans.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," Dr. Clegg said. "The notion that fat cells between males and females are alike is inconsistent with our findings."
In humans, men are more likely to carry extra weight around their guts while pre-menopausal women store it in their butts, thighs and hips. The bad news for men is that belly, or visceral, fat has been associated with numerous obesity-related diseases including diabetes and heart disease. Women, on the other hand, are generally protected from these obesity-related disorders until menopause, when their ovarian hormone levels drop and fat storage tends to shift from their rear ends to their waists.
"Although our new findings don't explain why women begin storing fat in their bellies after menopause, the results do bring us a step closer to understanding the mechanisms behind the unwanted shift," Dr. Clegg said.
For this study, researchers used a microarray analysis to determine whether male fat cells and female fat cells were different between the waist and hips and if they were different based on gender at a genetic level.
Because the fat distribution patterns of male and female mice are similar to those of humans, the researchers used the animals to compare genes from the belly and hip fat pads of male mice, female mice and female mice whose ovaries had been removed -- a condition that closely mimics human menopause. Waist and hip fat (subcutaneous fat) generally accumulates outside the muscle wall, whereas belly fat (visceral fat), a major health concern in men and postmenopausal women, develops around the internal organs.
In addition to the genetic differences among fat tissues, the researchers found that male mice that consumed a high-fat diet for 12 weeks gained more weight than female mice on the same diet. The males' fat tissue, particularly their belly fat, became highly inflamed, while the females had lower levels of genes associated with inflammation. The female mice whose ovaries had been removed, however, gained weight on the high-fat diet more like the males and deposited this fat in their bellies, also like the males.
"The fat of the female mice whose ovaries had been removed was inflamed and was starting to look like the unhealthy male fat," Dr. Clegg said. "However, estrogen replacement therapy in the mice reduced the inflammation and returned their fat distribution to that of mice with their ovaries intact."
Dr. Clegg said the results suggest that hormones made by the ovaries may be critical in determining where fat is deposited. Her overall goal is to determine how fat tissue is affected by sex hormones and whether it would be possible to develop a "designer" hormone replacement therapy that protected postmenopausal women from belly fat and related diseases such as metabolic syndrome...
"We found that out of about 40,000 mouse genes, only 138 are commonly found in both male and female fat cells," said Dr. Deborah Clegg, assistant professor of internal medicine at UT Southwestern Medical Center and senior author of the study appearing in the International Journal of Obesity. "This was completely unexpected. We expected the exact opposite -- that 138 would be different and the rest would be the same between the sexes."
The study involved mice, which distribute their fat in a sexually dimorphic pattern similar to humans.
"Given the difference in gene expression profiles, a female fat tissue won't behave anything like a male fat tissue and vice versa," Dr. Clegg said. "The notion that fat cells between males and females are alike is inconsistent with our findings."
In humans, men are more likely to carry extra weight around their guts while pre-menopausal women store it in their butts, thighs and hips. The bad news for men is that belly, or visceral, fat has been associated with numerous obesity-related diseases including diabetes and heart disease. Women, on the other hand, are generally protected from these obesity-related disorders until menopause, when their ovarian hormone levels drop and fat storage tends to shift from their rear ends to their waists.
"Although our new findings don't explain why women begin storing fat in their bellies after menopause, the results do bring us a step closer to understanding the mechanisms behind the unwanted shift," Dr. Clegg said.
For this study, researchers used a microarray analysis to determine whether male fat cells and female fat cells were different between the waist and hips and if they were different based on gender at a genetic level.
Because the fat distribution patterns of male and female mice are similar to those of humans, the researchers used the animals to compare genes from the belly and hip fat pads of male mice, female mice and female mice whose ovaries had been removed -- a condition that closely mimics human menopause. Waist and hip fat (subcutaneous fat) generally accumulates outside the muscle wall, whereas belly fat (visceral fat), a major health concern in men and postmenopausal women, develops around the internal organs.
In addition to the genetic differences among fat tissues, the researchers found that male mice that consumed a high-fat diet for 12 weeks gained more weight than female mice on the same diet. The males' fat tissue, particularly their belly fat, became highly inflamed, while the females had lower levels of genes associated with inflammation. The female mice whose ovaries had been removed, however, gained weight on the high-fat diet more like the males and deposited this fat in their bellies, also like the males.
"The fat of the female mice whose ovaries had been removed was inflamed and was starting to look like the unhealthy male fat," Dr. Clegg said. "However, estrogen replacement therapy in the mice reduced the inflammation and returned their fat distribution to that of mice with their ovaries intact."
Dr. Clegg said the results suggest that hormones made by the ovaries may be critical in determining where fat is deposited. Her overall goal is to determine how fat tissue is affected by sex hormones and whether it would be possible to develop a "designer" hormone replacement therapy that protected postmenopausal women from belly fat and related diseases such as metabolic syndrome...
Saturday, May 15, 2010
New way found to boost good cholesterol in mice
Two research teams have found a new way to increase levels of so-called "good" cholesterol in mice, they said on Thursday in a finding that could lead to better ways to prevent heart disease in humans...
Sunday, May 09, 2010
Slimming Aid from the Cell Laboratory? Inflammation Enzyme Regulates the Production of Brown Fat Tissue
Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have published an article in Science revealing that the COX-2 inflammation enzyme stimulates the formation of new brown fat tissue in mice. Brown fat tissue transforms energy into heat. Therefore, mice with increased COX-2 production have a higher energy consumption and are slimmer. On the basis of these results scientists might develop a novel weight loss method for pathogenic obesity.
Love handles, muffin tops and stomach tires -- white fat tissue forms the typical curves in the notorious problem areas to store energy. Exactly the opposite happens in brown fat tissue: Instead of being stored, energy gets transformed into heat. To the dismay of many people, adults have only small amounts of this energy burner. By contrast, babies and animals in hibernation have lots of it in their bodies where it serves for heat regulation.
Researchers know that external influences can stimulate the production of brown fat tissue in animals. If rodents are kept at low temperatures, clusters of brown fat cells form amid the white fat tissue. A DKFZ research team headed by Dr. Stephan Herzig, jointly with colleagues from Munich, Marburg, Frankfurt and Lausanne, has investigated the molecular causes of this phenomenon. They discovered that the production of the COX-2 inflammation enzyme is increased in white fat tissue of mice after exposure to cold temperatures. COX-2 is well known to scientists: It regulates the key step in the biosynthesis of prostaglandins -- inflammation-promoting hormones which are also responsible for activating pain...
Even without using cold temperatures the scientists were able to stimulate the formation of brown fat cell clusters in white fat tissue by boosting the COX-2 production in mice using a molecular-biological trick. The body weight of these animals was 20 percent lower than that of normal animals. Even on a calorie-rich diet they did not put on weight.
Love handles, muffin tops and stomach tires -- white fat tissue forms the typical curves in the notorious problem areas to store energy. Exactly the opposite happens in brown fat tissue: Instead of being stored, energy gets transformed into heat. To the dismay of many people, adults have only small amounts of this energy burner. By contrast, babies and animals in hibernation have lots of it in their bodies where it serves for heat regulation.
Researchers know that external influences can stimulate the production of brown fat tissue in animals. If rodents are kept at low temperatures, clusters of brown fat cells form amid the white fat tissue. A DKFZ research team headed by Dr. Stephan Herzig, jointly with colleagues from Munich, Marburg, Frankfurt and Lausanne, has investigated the molecular causes of this phenomenon. They discovered that the production of the COX-2 inflammation enzyme is increased in white fat tissue of mice after exposure to cold temperatures. COX-2 is well known to scientists: It regulates the key step in the biosynthesis of prostaglandins -- inflammation-promoting hormones which are also responsible for activating pain...
Even without using cold temperatures the scientists were able to stimulate the formation of brown fat cell clusters in white fat tissue by boosting the COX-2 production in mice using a molecular-biological trick. The body weight of these animals was 20 percent lower than that of normal animals. Even on a calorie-rich diet they did not put on weight.
Saturday, May 08, 2010
A potential new treatment for Type 2 diabetes
Australian scientists propose that a drug, already being used to treat rare inherited disorders, may also help people with Type 2 diabetes.
Type 2 diabetes occurs when the body no longer controls blood sugar levels properly. We need insulin, a hormone made in the pancreas, to channel sugar from our blood into our cells. The insulin-producing cells of the pancreas, known as ‘islets’ or ‘beta cells’, become progressively less efficient in people with Type 2 diabetes. At the same time, their muscles become less responsive to insulin, a condition known as ‘insulin resistance’. The combined result is high blood sugar levels, which can be very damaging to blood vessels and organs.
Kim Cheng and Drs Kenneth Ho and Jenny Gunton from Sydney’s Garvan Institute of Medical Research, show that the reduced expression of the HIF-1 alpha gene in beta cells – with the resulting reduction of HIF-1 alpha protein – helps explain the impaired ability of the pancreas to produce insulin in people with Type 2 diabetes. More importantly though, they were able to show that administering a drug (already approved for another rare disorder) increased levels of HIF-1 alpha protein and may restore insulin production. The findings are now online in the Journal of Clinical Investigation.
“We believe that HIF-1 alpha is a key player, effectively orchestrating many events in the cell that eventually start to shut down insulin secretion,” said Dr Gunton.
“HIF-1 alpha is a transcription factor, which means that it controls the way genes are expressed, or transcribed. This particular transcription factor happens to impact many genes that affect glucose uptake and metabolism in the pancreas. So when it is low, the beta cells have less energy.”
“Beta cells secrete insulin when they detect an increase in their own energy. When they can’t ‘see’ glucose, as rising energy, they don’t secrete insulin.”
The group tested and confirmed the importance of HIF-1 alpha in several ways.
First, they genetically engineered mice without the HIF-1 alpha gene in beta cells. These mice were mildly glucose intolerant, meaning that their blood sugar levels were higher than normal.
Next, they replicated the animal findings in cultured islets, in which the levels of HIF-1 alpha protein had been reduced.
After that, they fed genetically engineered and normal mice a high fat diet to make them fat and induce insulin resistance. Under these conditions, glucose levels deteriorate rapidly because beta cells are forced to work much harder to maintain normal sugar levels.
When all the mice were given the drug to stimulate the production of HIF-1 alpha protein, glucose levels improved in the ‘normal’ mice, despite the fact they continued on a high fat diet. The drug had absolutely no effect on the mice without the HIF-1 alpha gene in their beta cells.
“These tests left no doubt that it’s beta cell HIF-1 alpha that is needed for this drug to affect glucose tolerance,” said Gunton.
“Once we’d established that, we did a new study treating the ‘normal’ mice for six months to establish the drug’s safety over the longer-term. We did not detect side effects and the mice developed better glucose tolerance.”
“Then to be really thorough, we showed the same results in a completely different genetic line of mice.”
Type 2 diabetes occurs when the body no longer controls blood sugar levels properly. We need insulin, a hormone made in the pancreas, to channel sugar from our blood into our cells. The insulin-producing cells of the pancreas, known as ‘islets’ or ‘beta cells’, become progressively less efficient in people with Type 2 diabetes. At the same time, their muscles become less responsive to insulin, a condition known as ‘insulin resistance’. The combined result is high blood sugar levels, which can be very damaging to blood vessels and organs.
Kim Cheng and Drs Kenneth Ho and Jenny Gunton from Sydney’s Garvan Institute of Medical Research, show that the reduced expression of the HIF-1 alpha gene in beta cells – with the resulting reduction of HIF-1 alpha protein – helps explain the impaired ability of the pancreas to produce insulin in people with Type 2 diabetes. More importantly though, they were able to show that administering a drug (already approved for another rare disorder) increased levels of HIF-1 alpha protein and may restore insulin production. The findings are now online in the Journal of Clinical Investigation.
“We believe that HIF-1 alpha is a key player, effectively orchestrating many events in the cell that eventually start to shut down insulin secretion,” said Dr Gunton.
“HIF-1 alpha is a transcription factor, which means that it controls the way genes are expressed, or transcribed. This particular transcription factor happens to impact many genes that affect glucose uptake and metabolism in the pancreas. So when it is low, the beta cells have less energy.”
“Beta cells secrete insulin when they detect an increase in their own energy. When they can’t ‘see’ glucose, as rising energy, they don’t secrete insulin.”
The group tested and confirmed the importance of HIF-1 alpha in several ways.
First, they genetically engineered mice without the HIF-1 alpha gene in beta cells. These mice were mildly glucose intolerant, meaning that their blood sugar levels were higher than normal.
Next, they replicated the animal findings in cultured islets, in which the levels of HIF-1 alpha protein had been reduced.
After that, they fed genetically engineered and normal mice a high fat diet to make them fat and induce insulin resistance. Under these conditions, glucose levels deteriorate rapidly because beta cells are forced to work much harder to maintain normal sugar levels.
When all the mice were given the drug to stimulate the production of HIF-1 alpha protein, glucose levels improved in the ‘normal’ mice, despite the fact they continued on a high fat diet. The drug had absolutely no effect on the mice without the HIF-1 alpha gene in their beta cells.
“These tests left no doubt that it’s beta cell HIF-1 alpha that is needed for this drug to affect glucose tolerance,” said Gunton.
“Once we’d established that, we did a new study treating the ‘normal’ mice for six months to establish the drug’s safety over the longer-term. We did not detect side effects and the mice developed better glucose tolerance.”
“Then to be really thorough, we showed the same results in a completely different genetic line of mice.”
Australian researchers optimistic of new diabetes treatment
Australian researchers are hopeful they've found a new way to treat type 2 diabetes.
The World Health Organisation says in the Pacific, chronic diseases such as diabetes and cardiovascular diseases are among the most serious health problems.
The disease is associated with poor diet, lack of exercise and obesity.
In the study using mice, the researchers from Sydney's Garvin Institute of Medical Research found a way to switch on the insulin producing cells in the pancreas that all but stop working in people with diabetes...
The World Health Organisation says in the Pacific, chronic diseases such as diabetes and cardiovascular diseases are among the most serious health problems.
The disease is associated with poor diet, lack of exercise and obesity.
In the study using mice, the researchers from Sydney's Garvin Institute of Medical Research found a way to switch on the insulin producing cells in the pancreas that all but stop working in people with diabetes...
Scientists find anxiety gene that also makes you comfort eat
Researchers have found an "anxiety gene" which when switched on not only causes stress but increases our craving for sweets and comfort food.
They believe that the gene could be the reason why we are becoming an increasingly obese and stressful society. It could be the reason for the phenomenon "comfort eating".
Dr Alon Chen, a neuroendocrinologist at the Weizmann Institute in Israel, said: "We showed that the actions of a single gene in just one part of the brain can have profound effects on the metabolism of the whole body.
"In essence, stress may be turning us fat."
Few people lead stress-free lives these days which may, say experts, account for the rise in obesity triggered by the stress gene.
"Stress is definitely influencing every system in the body," said Dr Chen "It's not just causing anxiety, depression and post-traumatic stress disorder but is influencing metabolic syndromes such as obesity."
In the study, published in the Proceedings of the National Academy of Sciences, the researchers have discovered that there's a "stress switch" that seems to lead to diabetes and obesity.
The Israeli researchers created their own method for changing the activity of the gene in the brain, causing it to release varied amounts of a protein called Ucn3.
They discovered that increased levels of Ucn3 caused anxiety and changes in metabolism.
With increased levels of Ucn3, the bodies of mice used more sugar and less fatty acids and metabolic rates increased, showing the first stages of type 2 diabetes...
They believe that the gene could be the reason why we are becoming an increasingly obese and stressful society. It could be the reason for the phenomenon "comfort eating".
Dr Alon Chen, a neuroendocrinologist at the Weizmann Institute in Israel, said: "We showed that the actions of a single gene in just one part of the brain can have profound effects on the metabolism of the whole body.
"In essence, stress may be turning us fat."
Few people lead stress-free lives these days which may, say experts, account for the rise in obesity triggered by the stress gene.
"Stress is definitely influencing every system in the body," said Dr Chen "It's not just causing anxiety, depression and post-traumatic stress disorder but is influencing metabolic syndromes such as obesity."
In the study, published in the Proceedings of the National Academy of Sciences, the researchers have discovered that there's a "stress switch" that seems to lead to diabetes and obesity.
The Israeli researchers created their own method for changing the activity of the gene in the brain, causing it to release varied amounts of a protein called Ucn3.
They discovered that increased levels of Ucn3 caused anxiety and changes in metabolism.
With increased levels of Ucn3, the bodies of mice used more sugar and less fatty acids and metabolic rates increased, showing the first stages of type 2 diabetes...
Differences in disease risk for men and women start in the womb
Washington, DC: Disease risk in later life differs for women and men and now scientists have shown that this may start in the womb.
Pregnancy places competing demands on a mother's physiology: Her body wants to produce a strong healthy baby but not at the expense of her own health. Some of the genes that she passes on to her child therefore try to protect her own body from excessive demands from her child.
These so-called "imprinted genes" inherited from the father however do not show the same restraint - their goal is to get as many resources for the foetus as possible.
"The imprinted genes derived from the father are greedy whilst those from the mother are conservative in their needs to ensure future reproductive success", said Dr. Miguel Constancia from the University of Cambridge, England.
"We have found evidence that imprinted genes play important roles in the control of endocrine functions of the placenta. These placental adaptations have marked effects on nutrient delivery to the foetus, resulting in the programming of homeostatic mechanisms with metabolic consequences extending to adulthood, for example for type 2 diabetes susceptibility," Constancia added.
There is evidence that some programming effects are different in male and female offspring.
Dr. Rachel Dakin from the University of Edinburgh, Scotland, shows how maternal obesity is associated with sex-specific programming effects in young adult mice. Female offspring of obese mothers had raised blood insulin levels, whilst male offspring did not. Male offspring did have alterations in the expression of liver genes important in lipid and glucocorticoid metabolism...
Pregnancy places competing demands on a mother's physiology: Her body wants to produce a strong healthy baby but not at the expense of her own health. Some of the genes that she passes on to her child therefore try to protect her own body from excessive demands from her child.
These so-called "imprinted genes" inherited from the father however do not show the same restraint - their goal is to get as many resources for the foetus as possible.
"The imprinted genes derived from the father are greedy whilst those from the mother are conservative in their needs to ensure future reproductive success", said Dr. Miguel Constancia from the University of Cambridge, England.
"We have found evidence that imprinted genes play important roles in the control of endocrine functions of the placenta. These placental adaptations have marked effects on nutrient delivery to the foetus, resulting in the programming of homeostatic mechanisms with metabolic consequences extending to adulthood, for example for type 2 diabetes susceptibility," Constancia added.
There is evidence that some programming effects are different in male and female offspring.
Dr. Rachel Dakin from the University of Edinburgh, Scotland, shows how maternal obesity is associated with sex-specific programming effects in young adult mice. Female offspring of obese mothers had raised blood insulin levels, whilst male offspring did not. Male offspring did have alterations in the expression of liver genes important in lipid and glucocorticoid metabolism...
Study finds what makes calorie-burning "brown fat"
The discovery may help researchers develop ways to fight the obesity epidemic that is sucking up health budgets and resources in rich nations and quickly spreading to the developing world.
Stephan Herzig of the German Cancer Research Center in Heidelberg, who led the study, said scientists could now try using stem cells to generate brown fat cells in a lab dish to then implant them into the body and help speed up calorie burn.
"Now that we know some of the signals that are required to generate brown cells, we have the tools to put everything together and try it out," he said in a telephone interview.
Stem cells are the driver cells from which all other cells develop.
Rates of obesity have risen dramatically in recent decades in affluent nations, and more Western-style diets and less exercise mean that corpulence is taking hold in developing populations too.
Already, two-thirds of U.S. adults and nearly one in three children are overweight or obese -- a condition that increases risks of diabetes, heart disease and other chronic illnesses.
FOX-2 ENZYME IS THE TRIGGER
Experimenting on mice in the lab, Herzig and a team of scientists in Germany and Switzerland found that an enzyme called COX-2 triggers development of fat cells to become brown fat, instead of white fat.
White adipose tissue hoards fat by using our bodies -- particularly our bellies and thighs -- as a large storage unit, while brown adipose tissue is a sparse form of fat that helps keep newborns warm and helps adults burn calories.
Once activated by cold temperatures, brown fat burns calories faster than regular fat.
The researchers, whose study was published in the journal Science on Thursday, also found that mice who were genetically engineered to produce high levels of COX-2 burned energy faster and were protected from obesity.
Scientists estimate that as little as 50 grams of brown adipose tissue in a normal adult human would be enough to increase energy consumption by 20 percent...
Stephan Herzig of the German Cancer Research Center in Heidelberg, who led the study, said scientists could now try using stem cells to generate brown fat cells in a lab dish to then implant them into the body and help speed up calorie burn.
"Now that we know some of the signals that are required to generate brown cells, we have the tools to put everything together and try it out," he said in a telephone interview.
Stem cells are the driver cells from which all other cells develop.
Rates of obesity have risen dramatically in recent decades in affluent nations, and more Western-style diets and less exercise mean that corpulence is taking hold in developing populations too.
Already, two-thirds of U.S. adults and nearly one in three children are overweight or obese -- a condition that increases risks of diabetes, heart disease and other chronic illnesses.
FOX-2 ENZYME IS THE TRIGGER
Experimenting on mice in the lab, Herzig and a team of scientists in Germany and Switzerland found that an enzyme called COX-2 triggers development of fat cells to become brown fat, instead of white fat.
White adipose tissue hoards fat by using our bodies -- particularly our bellies and thighs -- as a large storage unit, while brown adipose tissue is a sparse form of fat that helps keep newborns warm and helps adults burn calories.
Once activated by cold temperatures, brown fat burns calories faster than regular fat.
The researchers, whose study was published in the journal Science on Thursday, also found that mice who were genetically engineered to produce high levels of COX-2 burned energy faster and were protected from obesity.
Scientists estimate that as little as 50 grams of brown adipose tissue in a normal adult human would be enough to increase energy consumption by 20 percent...
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