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...
Tuesday, July 27, 2010
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
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