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...
Saturday, July 10, 2010
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...
Friday, April 30, 2010
Gene that ties stress to diabetes, depression identified
Researchers have identified the gene changes in whose activity due to stress cause anxiety disorders and depression, as well as metabolic disorders like obesity, type 2 diabetes and arteriosclerosis.
These diseases, linked to stress, are reaching epidemic proportions.
Alon Chen of the Weizmann Institute's Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behaviour but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes...
These diseases, linked to stress, are reaching epidemic proportions.
Alon Chen of the Weizmann Institute's Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behaviour but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes...
Obesity epidemic blamed on bacteria
Previous research has shown that intestinal bacteria populations differ between the obese and the lean in humans. A new study using mice shows that increased appetite and insulin resistance can be transferred by intestinal bacteria from one mouse to another. This indicates that the presence of the intestinal bacterial contributes to changes in both appetite and metabolism.
The team at Emory were studying mice with an altered immune system so that they lacked Toll-like receptor 5 (TLR5), a receptor that recognises flagellin, and therefore the presence of bacteria. The TLR5 deficient mice were heavier than their normal counterparts and also consumed more food. They had metabolic changes associated with obesity. When the TLR5 deficient mice were fed a restricted diet, they remained insulin resistant. When given a full-fat diet, they developed diabetes and fatty liver disease. When TLR5 deficient mice were given strong antibiotics, enough to kill most of their intestinal flora, their metabolic abnormalities decreased. Studying the gut flora of TLR5 deficient mice and normal mice showed differing compositions of bacterial families. Previous research has already shown that the components of gut flora can alter the ability of the intestines to extract calories from food...
The team at Emory were studying mice with an altered immune system so that they lacked Toll-like receptor 5 (TLR5), a receptor that recognises flagellin, and therefore the presence of bacteria. The TLR5 deficient mice were heavier than their normal counterparts and also consumed more food. They had metabolic changes associated with obesity. When the TLR5 deficient mice were fed a restricted diet, they remained insulin resistant. When given a full-fat diet, they developed diabetes and fatty liver disease. When TLR5 deficient mice were given strong antibiotics, enough to kill most of their intestinal flora, their metabolic abnormalities decreased. Studying the gut flora of TLR5 deficient mice and normal mice showed differing compositions of bacterial families. Previous research has already shown that the components of gut flora can alter the ability of the intestines to extract calories from food...
Monday, April 26, 2010
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...
Saturday, April 24, 2010
Genetics in the Gut
Outnumbering our human cells by about 10 to one, the many minuscule microbes that live in and on our bodies are a big part of crucial everyday functions. The lion’s share live in the intestinal tract, where they help to fend off bad bacteria and aid in digestion. But as scientists determine what microbes are actually present and what they are doing, they are discovering that the bugs play an even larger role in human health than previously suspected—and perhaps at times exerting more influence than genes themselves.
A team that included Junjie Qin and Jun Wang of BGI-Shenzhen (formerly the Beijing Genomics Institute) completed a catalogue of some 3.3 million human gut microbe genes. The work, published in the March 4 Nature, adds to the expanding—but nowhere near complete—census of intestinal species. (Scientific American is part of Nature Publishing Group.)
The 3.3 million genes were a good deal “more than what we originally expected,” Wang says. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals the scientists sampled in Denmark and Spain. The team sequenced 576 billion base pairs, much larger than past work that found three billion base pairs. “These bacteria have functions that are essential to our health: they synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system,” Wang points out.
Another group, led by Andrew Gewirtz of Emory University, turned its attention to a particular host gene that seems to affect these intestinal inhabitants. It found that in mice, a loss of one key gene led to a shift in microbiota communities and a rise in insulin resistance, obesity and other symptoms of so-called metabolic syndrome (a cluster of these conditions).
Gewirtz and his co-workers studied mice bred with the genetic deficiency: an absence of Toll-like receptor 5, or TLR5, which has a hand in immune response. They wanted to see how it might change microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. “Obesity is associated with insulin resistance and type 2 diabetes,” Gewirtz says. But “which comes first is not entirely clear.”
As the researchers described in their paper published online March 4 by Science, they found that mice without the TLR5 gene—even when put on restricted diets—still showed insulin resistance, suggesting that the condition might lead to obesity rather than the other way around. But if these mice were allowed to eat as they pleased, they consumed 10 percent more than their peers and, by 20 weeks old, had body mass indexes that were 20 percent higher...
A team that included Junjie Qin and Jun Wang of BGI-Shenzhen (formerly the Beijing Genomics Institute) completed a catalogue of some 3.3 million human gut microbe genes. The work, published in the March 4 Nature, adds to the expanding—but nowhere near complete—census of intestinal species. (Scientific American is part of Nature Publishing Group.)
The 3.3 million genes were a good deal “more than what we originally expected,” Wang says. The number was especially surprising given that the microbiota tended to be very similar across the 124 individuals the scientists sampled in Denmark and Spain. The team sequenced 576 billion base pairs, much larger than past work that found three billion base pairs. “These bacteria have functions that are essential to our health: they synthesize vitamins, break down certain compounds—which cannot be assimilated by our body—[and] play an important role in our immune system,” Wang points out.
Another group, led by Andrew Gewirtz of Emory University, turned its attention to a particular host gene that seems to affect these intestinal inhabitants. It found that in mice, a loss of one key gene led to a shift in microbiota communities and a rise in insulin resistance, obesity and other symptoms of so-called metabolic syndrome (a cluster of these conditions).
Gewirtz and his co-workers studied mice bred with the genetic deficiency: an absence of Toll-like receptor 5, or TLR5, which has a hand in immune response. They wanted to see how it might change microbial gut communities and metabolic health—and try to understand the order in which the changes were happening. “Obesity is associated with insulin resistance and type 2 diabetes,” Gewirtz says. But “which comes first is not entirely clear.”
As the researchers described in their paper published online March 4 by Science, they found that mice without the TLR5 gene—even when put on restricted diets—still showed insulin resistance, suggesting that the condition might lead to obesity rather than the other way around. But if these mice were allowed to eat as they pleased, they consumed 10 percent more than their peers and, by 20 weeks old, had body mass indexes that were 20 percent higher...
Gene linking stress to obesity, diabetes discovered
Changes in the activity of a single gene in the brain can lead to metabolic changes that cause mice to develop symptoms associated with type 2 diabetes, as well as trigger anxious behavior.
These findings, discovered by Weizmann Institute of Science researchers, were published online this week in the Proceedings of the National Academy of Sciences (PNAS).
The constant stress many are exposed to in our modern society may thus be taking a heavy toll: Anxiety disorders and depression, as well as metabolic disorders such as obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress.
These problems are reaching epidemic proportions. Type 2 diabetes alone is expected to affect some 360 million people around the world in 20 years.
The connection between stress, changes in appetite and anxiety-related behavior was recently proven scientifically, but the exact reasons for this were not clear until Dr. Alon Chen of the Rehovot institute’s neurobiology department and colleagues made their gene discovery.
They found that all the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes in the metabolism of various substances and even changes in food preferences.
The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved in tying all of these together. Produced in certain brain cells – especially in times of stress – it is known to play a role in regulating the body’s stress response.
These nerve cells have extensions that act as “highways” to speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions – oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including anxiety levels...
These findings, discovered by Weizmann Institute of Science researchers, were published online this week in the Proceedings of the National Academy of Sciences (PNAS).
The constant stress many are exposed to in our modern society may thus be taking a heavy toll: Anxiety disorders and depression, as well as metabolic disorders such as obesity, type 2 diabetes and arteriosclerosis, have all been linked to stress.
These problems are reaching epidemic proportions. Type 2 diabetes alone is expected to affect some 360 million people around the world in 20 years.
The connection between stress, changes in appetite and anxiety-related behavior was recently proven scientifically, but the exact reasons for this were not clear until Dr. Alon Chen of the Rehovot institute’s neurobiology department and colleagues made their gene discovery.
They found that all the body’s systems are involved in the stress response, which evolved to deal with threats and danger. Behavioral changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat-generation, changes in the metabolism of various substances and even changes in food preferences.
The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved in tying all of these together. Produced in certain brain cells – especially in times of stress – it is known to play a role in regulating the body’s stress response.
These nerve cells have extensions that act as “highways” to speed Ucn3 on to two other sites in the brain: One, in the hypothalamus – the brain’s center for hormonal regulation of basic bodily functions – oversees, among other things, substance exchange and feelings of hunger and satiety; the other is involved in regulating behavior, including anxiety levels...
Sunday, April 18, 2010
Mice With High-Altitude Metabolism Stay Slim And Healthy On A High-Fat Diet
Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found.
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said...
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said...
Thursday, April 15, 2010
High-Altitude Metabolism Lets Mice Stay Slim and Healthy on a High-Fat Diet
Mice that are missing a protein involved in the response to low oxygen stay lean and healthy, even on a high-fat diet, a new study has found.
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said.
Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.
"We expected them to die as embryos," said Na Zhang, a graduate student in Johnson's lab and lead author of the study. "Then we saw they can survive for a long time."
"From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy," Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.
"We fed the mice with a very high fat diet -- 60 percent fat -- just to see how they would respond," Zhang said. "Mutants can eat a lot, but they didn't gain a lot of weight. They are less fatty around their middles compared with their littermates."
Obese people develop a "fatty liver," and so did the wild type littermates. The fat mice also developed high blood cholesterol with elevated levels of the "bad" type, LDL. In lean mutants, LDL increased much less.
"All of these observations support that the modified mice have better metabolic profiles," Zhang said...
"They process fat differently," said Randall Johnson, professor of biology at the University of California, San Diego, who directed the research, which is published in the April 15 issue of the journal Cell Metabolism. While their normal littermates gain weight, develop fatty livers and become resistant to insulin on a high fat diet, just like overweight humans do, the mutant mice suffered none of these ill effects.
The protein, an enzyme called FIH, plays a key role in the physiological response to low levels of oxygen and could be a new target for drugs to help people who struggle with weight gain. "The enzyme is easily inhibited by drugs," Johnson said.
Because the protein influences a wide range of genes involved in development, the scientists were surprised that its deletion improved health.
"We expected them to die as embryos," said Na Zhang, a graduate student in Johnson's lab and lead author of the study. "Then we saw they can survive for a long time."
"From the beginning I noticed that these mice are smaller, but not sick. These mice seem to be healthy," Zhang said. The lean mice have a high metabolism, and a common check for insulin resistance, a symptom of diabetes, revealed a super sensitivity to insulin.
"We fed the mice with a very high fat diet -- 60 percent fat -- just to see how they would respond," Zhang said. "Mutants can eat a lot, but they didn't gain a lot of weight. They are less fatty around their middles compared with their littermates."
Obese people develop a "fatty liver," and so did the wild type littermates. The fat mice also developed high blood cholesterol with elevated levels of the "bad" type, LDL. In lean mutants, LDL increased much less.
"All of these observations support that the modified mice have better metabolic profiles," Zhang said...
Wednesday, April 14, 2010
Brent Batten: Jackson Lab a meeting of mice and men
Move over Mickey.
There’s a new mouse in town. Or at least there will be if Jackson Laboratory can secure the money it’s seeking to build a research facility in Florida.
Mickey’s been the state’s main mouse since 1971 when Walt Disney World opened in Orlando but the Jackson Lab brings with it not only a reputation for doing cutting edge genetic research but also one as the world’s foremost breeder of mice. Or, more accurately, it brings a reputation for doing cutting edge genetic research because it is the world’s foremost breeder of mice.
The Florida facility, planned for eastern Collier County providing the right combination of state, local and private funding can be found, would mainly use computers and not be as mouse-intensive as Jackson’s Bar Harbor, Maine, headquarters, but the work done here would build on nearly a century of experience with the rodent.
Jackson Lab founder C.C. Little in 1929 had a vision for researching the genetic aspects of cancer. At the time, the genetic study of mice had been underway for about 30 years. Little is credited with conceiving of and creating the first inbred strain of laboratory mice to unravel the genetics of cancer.
Today, Jackson Labs maintains about 5,000 different strains of inbred mice. They are used both for research in the lab and for sale to scientists around the world. Do you need an obese mouse with a strong immunity to pancreatic cancer? Jackson can hook you up. A diabetic mouse with lymphoma? Got it. Or, if they don’t, they’ll try to create it for you.
Last year Jackson sold, on a nonprofit basis, about 2.5 million mice to 16,000 labs in 53 countries, according to Joyce Peterson, communications manager for the laboratory. Sixteen Jackson Lab mice are in orbit right now, ferried to the International Space Station by Discovery for an experiment on the effects of space on the immune system.
At any given time there might be 750,000 mice at the Bar Harbor campus. For-profit labs also breed and sell mice but they tend to stock only a few dozen strains, those that are most popular, Peterson said.
“The 20,000 genes that make up humans and mice are pretty much the same,” said Rich Woychik, president of Jackson Labs. “Mice develop the same types of cancer humans develop. We can basically study these things with the mouse.”
Woychik said Florida has been very welcoming to bio-tech companies, an attitude that led Jackson to choose it over offers from places like Boston and Salt Lake City. The work of the Collier County Economic Development Council further steered the lab toward Southwest Florida. “There’s been tremendous enthusiasm in the state for major biomedical investment. Those investments are beginning to pay off,” Woychik said, adding of Collier County, “We really like your community.”
These days, researchers can manipulate the genes of mice to get the combinations they want. “We can essentially swap out genes and exchange them at will,” Woychik said.
But for decades the work was more laborious. Identical mice would be bred, and researchers would look carefully for differences _ mutations _ in their offspring. That sort of work is still done, Peterson said. Mutants are separated and checked every two weeks as scientists look for traits that might make them useful in studying a particular disease. A heavy mouse might come in handy in the study of obesity or diabetes, for instance.
There’s a new mouse in town. Or at least there will be if Jackson Laboratory can secure the money it’s seeking to build a research facility in Florida.
Mickey’s been the state’s main mouse since 1971 when Walt Disney World opened in Orlando but the Jackson Lab brings with it not only a reputation for doing cutting edge genetic research but also one as the world’s foremost breeder of mice. Or, more accurately, it brings a reputation for doing cutting edge genetic research because it is the world’s foremost breeder of mice.
The Florida facility, planned for eastern Collier County providing the right combination of state, local and private funding can be found, would mainly use computers and not be as mouse-intensive as Jackson’s Bar Harbor, Maine, headquarters, but the work done here would build on nearly a century of experience with the rodent.
Jackson Lab founder C.C. Little in 1929 had a vision for researching the genetic aspects of cancer. At the time, the genetic study of mice had been underway for about 30 years. Little is credited with conceiving of and creating the first inbred strain of laboratory mice to unravel the genetics of cancer.
Today, Jackson Labs maintains about 5,000 different strains of inbred mice. They are used both for research in the lab and for sale to scientists around the world. Do you need an obese mouse with a strong immunity to pancreatic cancer? Jackson can hook you up. A diabetic mouse with lymphoma? Got it. Or, if they don’t, they’ll try to create it for you.
Last year Jackson sold, on a nonprofit basis, about 2.5 million mice to 16,000 labs in 53 countries, according to Joyce Peterson, communications manager for the laboratory. Sixteen Jackson Lab mice are in orbit right now, ferried to the International Space Station by Discovery for an experiment on the effects of space on the immune system.
At any given time there might be 750,000 mice at the Bar Harbor campus. For-profit labs also breed and sell mice but they tend to stock only a few dozen strains, those that are most popular, Peterson said.
“The 20,000 genes that make up humans and mice are pretty much the same,” said Rich Woychik, president of Jackson Labs. “Mice develop the same types of cancer humans develop. We can basically study these things with the mouse.”
Woychik said Florida has been very welcoming to bio-tech companies, an attitude that led Jackson to choose it over offers from places like Boston and Salt Lake City. The work of the Collier County Economic Development Council further steered the lab toward Southwest Florida. “There’s been tremendous enthusiasm in the state for major biomedical investment. Those investments are beginning to pay off,” Woychik said, adding of Collier County, “We really like your community.”
These days, researchers can manipulate the genes of mice to get the combinations they want. “We can essentially swap out genes and exchange them at will,” Woychik said.
But for decades the work was more laborious. Identical mice would be bred, and researchers would look carefully for differences _ mutations _ in their offspring. That sort of work is still done, Peterson said. Mutants are separated and checked every two weeks as scientists look for traits that might make them useful in studying a particular disease. A heavy mouse might come in handy in the study of obesity or diabetes, for instance.
A New Way to Lose Weight?
In the quest to fight obesity, scientists are looking at an intriguing question: Is it possible for adults to lose weight by having more baby fat?
Babies have lots of brown adipose tissue, or brown fat, so called because of its color. It is critical to the body's heat production. Unlike white fat cells, which store energy from the food we eat, brown fat consumes calories to generate heat. Revving up this process, research has shown, may help us grow leaner by burning more of the white fat.
Until recently, experts believed that only babies and children had brown fat, to help keep them warm before their young bodies develop techniques like shivering to help them cope with cold temperatures. A discovery last year that adults still have at least some brown fat has spawned hope among scientists and drug developers that the calorie-burning tissue may provide one solution to curbing obesity.
Researchers at Harvard Medical School have identified a protein in the body that appears to spur production of brown fat, including by converting some white fat cells into brown ones, and are now working to develop a drug that would encourage that process. They expect their work could lead to a new approach to treating obesity within a few years.
Other researchers are seeking ways to prompt the brown fat we already have to become more active, thereby prompting our bodies to generate more heat and consume more calories. One technique being investigated: exposing people to colder temperatures, which appears to trigger brown fat to turn up the body's heat.
"The obesity problem continues to be a real time bomb in the United States and in many other countries in the world," says Bruce Spiegelman, a professor of cell biology and medicine at Harvard's Dana-Farber Cancer Center in Boston. "We're not trying to replace diet and exercise, but frequently they're not enough or not effective."
Dr. Spiegelman and his team in 2007 discovered a protein called PRDM16 that appears to regulate the production of brown fat. Mice without PRDM16 don't form good, working brown fat cells, while those with PRDM16 do, studies showed. The researchers then genetically altered some mice so that they would produce greater amounts of PRDM16. The mice's heat generation and calorie-burning rate went up, too, according to research they published in the journal Nature in 2008...
Babies have lots of brown adipose tissue, or brown fat, so called because of its color. It is critical to the body's heat production. Unlike white fat cells, which store energy from the food we eat, brown fat consumes calories to generate heat. Revving up this process, research has shown, may help us grow leaner by burning more of the white fat.
Until recently, experts believed that only babies and children had brown fat, to help keep them warm before their young bodies develop techniques like shivering to help them cope with cold temperatures. A discovery last year that adults still have at least some brown fat has spawned hope among scientists and drug developers that the calorie-burning tissue may provide one solution to curbing obesity.
Researchers at Harvard Medical School have identified a protein in the body that appears to spur production of brown fat, including by converting some white fat cells into brown ones, and are now working to develop a drug that would encourage that process. They expect their work could lead to a new approach to treating obesity within a few years.
Other researchers are seeking ways to prompt the brown fat we already have to become more active, thereby prompting our bodies to generate more heat and consume more calories. One technique being investigated: exposing people to colder temperatures, which appears to trigger brown fat to turn up the body's heat.
"The obesity problem continues to be a real time bomb in the United States and in many other countries in the world," says Bruce Spiegelman, a professor of cell biology and medicine at Harvard's Dana-Farber Cancer Center in Boston. "We're not trying to replace diet and exercise, but frequently they're not enough or not effective."
Dr. Spiegelman and his team in 2007 discovered a protein called PRDM16 that appears to regulate the production of brown fat. Mice without PRDM16 don't form good, working brown fat cells, while those with PRDM16 do, studies showed. The researchers then genetically altered some mice so that they would produce greater amounts of PRDM16. The mice's heat generation and calorie-burning rate went up, too, according to research they published in the journal Nature in 2008...
A New Take on Obesity's Origins
Here's a word that could rock your world: epigenetics.
No, that's not the latest cosmetic treatment for wrinkles, or a cool new weight loss technique — although it does have to do with body weight.
"Epigenetics" means "on or above genetics." And when what's called an "epigenetics mechanism" is at work in a living organism, the genes themselves aren't altered, but how the genes function during the organism's early growth is changed.
This is starting to sound too much like a science class, so let's back up a bit and put this in more human terms.
You're probably aware that when women are pregnant, they often hear from their doctors the mantra, "Don't gain too much weight during your pregnancy." What constitutes "too much" has probably changed over the years, but doctors don't find that old "eating for two" excuse as cute as the rest of us might. In fact, doctors are also advising women who want to become pregnant to get to a healthy weight before doing so.
This isn't just the typical medical "tut-tut-ing," as it turns out. Studies funded by the Agricultural Research Service (ARS) are giving us a new and somewhat startling look at how influences that occur in the womb and perhaps during the first few months of life could affect development of a child's ability to regulate his or her weight, even into adulthood.
Yes, you read that right: If a woman packs on too many pounds during pregnancy, the child's body-weight-regulating mechanism could be harmed by the mom's excess weight. This, in turn, could increase the risk that the child would become an overweight or obese adult, with a higher risk of health problems such as type 2 diabetes or cardiovascular disease.
In the ARS-funded study, scientists looked at weight gains among rat pups whose mothers, called "dams," were either lean or overweight (as a result of deliberate overfeeding in the laboratory) at the time of conception and during pregnancy.
For this study, the scientists mated the lean or overweight female rats with lean males. The pups were nursed only by normal-weight dams to make sure the pups' exposure to their mothers' obesity occurred only in the womb.
All of the rat pups were at a normal weight at birth and at weaning. But when the weaned offspring were given free access to a high-fat ration, the offspring born to overweight mothers gained significantly more weight, and more of that weight as fat, compared to the offspring of the lean mothers. And that's despite the fact that the offspring of the overweight mothers didn't eat any more of the high-fat food than did the pups born to the lean mothers!
What does this mean in real-world terms? The study's results strongly suggest that exposure to the mother's obesity — while in the womb — results in programming of the baby's body-weight-control mechanisms. The factor of the mother's obesity all by itself was enough to significantly increase the baby rats' susceptibility to obesity.
You might be thinking, "Well, maybe those rats were genetically different from each other, so that's why this happened." But the scientists were careful to use only rats that were genetically similar, so that rules out the possibility that genetic differences among the mothers could contribute to the remarkable difference in the baby rats' sensitivity to those high-fat rations.
If this all translates to humans, this study's findings underscore the need for women who want to become pregnant to make sure they're at a healthy weight at conception, and to gain no more than the recommended amount of weight during the pregnancy. Unfortunately, the incidence of obesity or overweight among pregnant women in the United States is on the rise.
What's more, an epigenetics study from 2008 with a population of genetically similar lab mice with a tendency toward obesity showed a "transgenerational amplification of obesity." That means that the overweight mouse mothers gave birth to even heavier baby mice, the females of which gave birth to still heavier baby mice — and on unto the third generation...
No, that's not the latest cosmetic treatment for wrinkles, or a cool new weight loss technique — although it does have to do with body weight.
"Epigenetics" means "on or above genetics." And when what's called an "epigenetics mechanism" is at work in a living organism, the genes themselves aren't altered, but how the genes function during the organism's early growth is changed.
This is starting to sound too much like a science class, so let's back up a bit and put this in more human terms.
You're probably aware that when women are pregnant, they often hear from their doctors the mantra, "Don't gain too much weight during your pregnancy." What constitutes "too much" has probably changed over the years, but doctors don't find that old "eating for two" excuse as cute as the rest of us might. In fact, doctors are also advising women who want to become pregnant to get to a healthy weight before doing so.
This isn't just the typical medical "tut-tut-ing," as it turns out. Studies funded by the Agricultural Research Service (ARS) are giving us a new and somewhat startling look at how influences that occur in the womb and perhaps during the first few months of life could affect development of a child's ability to regulate his or her weight, even into adulthood.
Yes, you read that right: If a woman packs on too many pounds during pregnancy, the child's body-weight-regulating mechanism could be harmed by the mom's excess weight. This, in turn, could increase the risk that the child would become an overweight or obese adult, with a higher risk of health problems such as type 2 diabetes or cardiovascular disease.
In the ARS-funded study, scientists looked at weight gains among rat pups whose mothers, called "dams," were either lean or overweight (as a result of deliberate overfeeding in the laboratory) at the time of conception and during pregnancy.
For this study, the scientists mated the lean or overweight female rats with lean males. The pups were nursed only by normal-weight dams to make sure the pups' exposure to their mothers' obesity occurred only in the womb.
All of the rat pups were at a normal weight at birth and at weaning. But when the weaned offspring were given free access to a high-fat ration, the offspring born to overweight mothers gained significantly more weight, and more of that weight as fat, compared to the offspring of the lean mothers. And that's despite the fact that the offspring of the overweight mothers didn't eat any more of the high-fat food than did the pups born to the lean mothers!
What does this mean in real-world terms? The study's results strongly suggest that exposure to the mother's obesity — while in the womb — results in programming of the baby's body-weight-control mechanisms. The factor of the mother's obesity all by itself was enough to significantly increase the baby rats' susceptibility to obesity.
You might be thinking, "Well, maybe those rats were genetically different from each other, so that's why this happened." But the scientists were careful to use only rats that were genetically similar, so that rules out the possibility that genetic differences among the mothers could contribute to the remarkable difference in the baby rats' sensitivity to those high-fat rations.
If this all translates to humans, this study's findings underscore the need for women who want to become pregnant to make sure they're at a healthy weight at conception, and to gain no more than the recommended amount of weight during the pregnancy. Unfortunately, the incidence of obesity or overweight among pregnant women in the United States is on the rise.
What's more, an epigenetics study from 2008 with a population of genetically similar lab mice with a tendency toward obesity showed a "transgenerational amplification of obesity." That means that the overweight mouse mothers gave birth to even heavier baby mice, the females of which gave birth to still heavier baby mice — and on unto the third generation...
Wednesday, April 07, 2010
Experts to design molecule to shut down fat gene
Scientists in China may have discovered how a gene responsible for obesity kicks into action and want to design a molecule to shut it down.
The fat mass and obesity-associated gene (FTO) sits on human chromosome 16, and several studies in the past have shown it is strongly linked to weight gain. But scientists are just beginning to figure out how the gene actually works.
"This gene was identified through studies done among different ethnic groups -- Caucasions, Chinese, Japanese and (South) Koreans. It has been established that FTO is associated with obesity," Jijie Chai at the National Institute of Biological Sciences in Beijing told Reuters by telephone.
"We believe that FTO is a good target for treatment of obesity. If we can get an active inhibitor (to shut down the FTO gene), we can work toward some sort of therapy."
In a paper published in the latest issue of Nature, lead researcher Chai and his colleagues described how their study found the FTO gene was only activated when it binds to what are known as "single-stranded DNA".
"It has only activity toward single-stranded DNA and has no activity toward double-stranded DNA," Chai said.
"We want to design a small molecule to block FTO activity, to shut down its function. We can feed this (molecule) to mice and see what happens. If the mice get leaner, that would be very exciting," Chai said, but he added that any therapy for obesity would be years away...
The fat mass and obesity-associated gene (FTO) sits on human chromosome 16, and several studies in the past have shown it is strongly linked to weight gain. But scientists are just beginning to figure out how the gene actually works.
"This gene was identified through studies done among different ethnic groups -- Caucasions, Chinese, Japanese and (South) Koreans. It has been established that FTO is associated with obesity," Jijie Chai at the National Institute of Biological Sciences in Beijing told Reuters by telephone.
"We believe that FTO is a good target for treatment of obesity. If we can get an active inhibitor (to shut down the FTO gene), we can work toward some sort of therapy."
In a paper published in the latest issue of Nature, lead researcher Chai and his colleagues described how their study found the FTO gene was only activated when it binds to what are known as "single-stranded DNA".
"It has only activity toward single-stranded DNA and has no activity toward double-stranded DNA," Chai said.
"We want to design a small molecule to block FTO activity, to shut down its function. We can feed this (molecule) to mice and see what happens. If the mice get leaner, that would be very exciting," Chai said, but he added that any therapy for obesity would be years away...
UT Southwestern scientists unravel brain-hormone circuit that helps police diabetes, female fertility
New findings by UT Southwestern Medical Center researchers suggest that the hormones leptin and insulin work together in specific neurons in the hypothalamus region of the brain to affect both the regulation of blood sugar levels in the body and, surprisingly, female fertility.
"Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, which appears online and in the current issue of Cell Metabolism. "Our findings indicate that is not necessarily the case, at least in mice...
"Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, which appears online and in the current issue of Cell Metabolism. "Our findings indicate that is not necessarily the case, at least in mice...
Friday, April 02, 2010
Revolutionary capsule offers hope to diabetics
London: A revolutionary technique that has been found to successfully treat the symptoms of gout could result in a new form of therapy for a range of other medical conditions - such as diabetes and obesity, say experts.
Gout is caused by a build up of uric acid in the bloodstream, which results in crystals of uric acid being deposited in the kidneys and joints, leading to bouts of extreme pain.
Professor Martin Fussenegger of the Swiss Federal Institute of Technology in Zurich designed a 'molecular prosthesis' to treat gout, which is made from human cells designed to detect an increase in levels of uric acid and to respond by secreting an enzyme called urate oxydase, which destroys uric acid.
The treatment consists of implanting a small plastic capsule under the skin, which is loaded with genetically engineered cells taken from the patients themselves.
The capsule effectively works as a synthetic organ balancing the body's chemicals and hormones.
"We have constructed a synthetic genetic circuitry that can detect uric acid in the bloodstream and process this information to produce a therapeutic response," the Independent quoted Fussenegger as saying.
Tests on laboratory mice have proved the efficacy of the new technique...
Gout is caused by a build up of uric acid in the bloodstream, which results in crystals of uric acid being deposited in the kidneys and joints, leading to bouts of extreme pain.
Professor Martin Fussenegger of the Swiss Federal Institute of Technology in Zurich designed a 'molecular prosthesis' to treat gout, which is made from human cells designed to detect an increase in levels of uric acid and to respond by secreting an enzyme called urate oxydase, which destroys uric acid.
The treatment consists of implanting a small plastic capsule under the skin, which is loaded with genetically engineered cells taken from the patients themselves.
The capsule effectively works as a synthetic organ balancing the body's chemicals and hormones.
"We have constructed a synthetic genetic circuitry that can detect uric acid in the bloodstream and process this information to produce a therapeutic response," the Independent quoted Fussenegger as saying.
Tests on laboratory mice have proved the efficacy of the new technique...
An apple a day...
Researchers from the University of Illinois fed laboratory mice low-fat diets that were identical, except that they contained either soluble or insoluble fibre. They found that soluble fibre reduces inflammation associated with obesity-related diseases and strengthens the immune system.
“Soluble fibre changes the personality of immune cells – they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection,” said Gregory Freund, professor at the college of medicine...
“Soluble fibre changes the personality of immune cells – they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection,” said Gregory Freund, professor at the college of medicine...
Overcoming Obesity
For dieters, it's sometimes impossible to resist your favorite foods. Like chocolate. And now some researchers working with mice think they have a clue as to why the temptation can get so strong.
After starving mice of food, scientists presented them with a highly desirable treat of chocolate — in an experiment designed to keep them from getting it. Each time the animals went for the sweet, they received a small foot shock. One group of starving mice learned to stop reaching for the chocolate after a few shocks, but another group went for the candy relentlessly, despite the negative consequences.
The difference between the two groups seemed to be levels of norepinephrine, a hormone and neurotransmitter released in the prefrontal cortex of the brain, which is involved in reward and satiety circuits. Norepinephrine plays an important role in compulsive behaviors associated with drug abuse, and also contributes to food-seeking behavior. In the chocolate trial, the treat-seeking mice had higher levels of norepinephrine than the mice who abandoned the chocolate. And when scientists used an inhibitor to inactivate the chemical in the chocolate-obsessed animals, their compulsive behavior stopped.
Doctors hope that by understanding the way biological processes reinforce maladaptive behaviors like obsessive eating, they can focus on new targets for treating obesity — targets that directly address the root causes of why some people continue to eat, even when they know they shouldn't.
After starving mice of food, scientists presented them with a highly desirable treat of chocolate — in an experiment designed to keep them from getting it. Each time the animals went for the sweet, they received a small foot shock. One group of starving mice learned to stop reaching for the chocolate after a few shocks, but another group went for the candy relentlessly, despite the negative consequences.
The difference between the two groups seemed to be levels of norepinephrine, a hormone and neurotransmitter released in the prefrontal cortex of the brain, which is involved in reward and satiety circuits. Norepinephrine plays an important role in compulsive behaviors associated with drug abuse, and also contributes to food-seeking behavior. In the chocolate trial, the treat-seeking mice had higher levels of norepinephrine than the mice who abandoned the chocolate. And when scientists used an inhibitor to inactivate the chemical in the chocolate-obsessed animals, their compulsive behavior stopped.
Doctors hope that by understanding the way biological processes reinforce maladaptive behaviors like obsessive eating, they can focus on new targets for treating obesity — targets that directly address the root causes of why some people continue to eat, even when they know they shouldn't.
Novel Method Eyed for Normalizing Blood Sugar
A potential new method of normalizing blood sugar levels in diabetes has been discovered by U.S. researchers.
The Children's Hospital Boston team identified a cellular pathway that fails because of obesity. Artificial activation of this pathway normalized glucose levels in severely obese and diabetic mice, according to the report published online March 28 in Nature Medicine.
Previously, the researchers found that the brain, liver and fat cells of obese mice have increased stress in the endoplasmic reticulum (ER), which produces proteins. Obesity overwhelms the ER and causes it to malfunction. This so-called "ER stress" triggers a series of events that suppresses the body's response to insulin, making ER stress an important link between obesity and type 2 diabetes...
The Children's Hospital Boston team identified a cellular pathway that fails because of obesity. Artificial activation of this pathway normalized glucose levels in severely obese and diabetic mice, according to the report published online March 28 in Nature Medicine.
Previously, the researchers found that the brain, liver and fat cells of obese mice have increased stress in the endoplasmic reticulum (ER), which produces proteins. Obesity overwhelms the ER and causes it to malfunction. This so-called "ER stress" triggers a series of events that suppresses the body's response to insulin, making ER stress an important link between obesity and type 2 diabetes...
Addicted to Fat: Overeating May Alter the Brain as Much as Hard Drugs
Like many people, rats are happy to gorge themselves on tasty, high-fat treats. Bacon, sausage, chocolate and even cheesecake quickly became favorites of laboratory rats that recently were given access to these human indulgences—so much so that the animals came to depend on high quantities to feel good, like drug users who need to up their intake to get high.
A new study, published online March 28 in Nature Neuroscience, describes these rats' indulgent tribulations, adding to research literature on the how excess food intake can trigger changes in the brain, alterations that seem to create a neurochemical dependency in the eater—or user. (Scientific American is part of Nature Publishing Group.) Preliminary findings from the work were presented at the Society for Neuroscience meeting in October 2009...
A new study, published online March 28 in Nature Neuroscience, describes these rats' indulgent tribulations, adding to research literature on the how excess food intake can trigger changes in the brain, alterations that seem to create a neurochemical dependency in the eater—or user. (Scientific American is part of Nature Publishing Group.) Preliminary findings from the work were presented at the Society for Neuroscience meeting in October 2009...
Fried breakfast is healthiest start to day, say scientists
Scientists believe that breakfast programmes the metabolism for the rest of the day, and a fatty meal will help the body break down fat later on.
Carbohydrate rich foods in contrast appear mainly to prepare the body to break down only carbohydrates, the International Journal of Obesity reports.
Dr Martin Young, of the University of Alabama at Birmingham, said: “The first meal you have appears to programme your metabolism for the rest of the day.
“This study suggests that if you ate a carbohydrate-rich breakfast it would promote carbohydrate utilisation throughout the rest of the day, whereas if you have a fat-rich breakfast, you (can) transfer your energy utilisation between carbohydrate and fat.”
The team of researchers found there may be some truth in the old saying “'eat breakfast like a king, lunch like a prince and dinner like a pauper' – may be the key to a healthy body and mind.”
Their study looked at the effects of eating different types of food – and of eating them at different times in the day, according to the Daily Mail.
Mice fed a high fat meal after waking remained healthy, but those given a carb-rich breakfast, followed by a fatty dinner, did not fare as well...
Carbohydrate rich foods in contrast appear mainly to prepare the body to break down only carbohydrates, the International Journal of Obesity reports.
Dr Martin Young, of the University of Alabama at Birmingham, said: “The first meal you have appears to programme your metabolism for the rest of the day.
“This study suggests that if you ate a carbohydrate-rich breakfast it would promote carbohydrate utilisation throughout the rest of the day, whereas if you have a fat-rich breakfast, you (can) transfer your energy utilisation between carbohydrate and fat.”
The team of researchers found there may be some truth in the old saying “'eat breakfast like a king, lunch like a prince and dinner like a pauper' – may be the key to a healthy body and mind.”
Their study looked at the effects of eating different types of food – and of eating them at different times in the day, according to the Daily Mail.
Mice fed a high fat meal after waking remained healthy, but those given a carb-rich breakfast, followed by a fatty dinner, did not fare as well...
Wednesday, March 24, 2010
How Weight-Loss Surgery Reverses Type 2 Diabetes: New Study Offers Explanation
A team of researchers, led by a UC Davis veterinary endocrinologist, has shown for the first time that a surgical procedure in rats that is similar to bariatric surgery in humans can delay the onset of type 2 diabetes. The researchers also have identified biochemical changes caused by the surgeries that may be responsible for that delay...
Friday, March 19, 2010
Why tangy fruit could stop you gaining weight
The secret to staying slim may lie in a tangy fruit.
The juice of the blood orange stops mice piling on weight when fed a high-fat diet, research shows.
In contrast, mice fed sweeter oranges more popular in the UK gain significant amounts of fat.
Scientists believe the fat-busting powers of the fruit, grown in Italy and the U.S., may be partly due to its high levels of anthocyanin. This red pigment that gives the orange its deep colour is a type of antioxidant, a natural chemical that helps ward off disease.
The juice damages the ability of cells called adipocytes to accumulate fat, University of Milan researchers told the International Journal of Obesity.
Adipocytes are found mostly around the waistline and absorb fat from food to store as energy.
The juice of the blood orange stops mice piling on weight when fed a high-fat diet, research shows.
In contrast, mice fed sweeter oranges more popular in the UK gain significant amounts of fat.
Scientists believe the fat-busting powers of the fruit, grown in Italy and the U.S., may be partly due to its high levels of anthocyanin. This red pigment that gives the orange its deep colour is a type of antioxidant, a natural chemical that helps ward off disease.
The juice damages the ability of cells called adipocytes to accumulate fat, University of Milan researchers told the International Journal of Obesity.
Adipocytes are found mostly around the waistline and absorb fat from food to store as energy.
Mom’s Obesity Influences Kid’s Weight
Scientists at two ARS-funded nutrition research centers are examining how maternal influences of the unborn child and the developing newborn could increase the risk that the child would become an overweight or obese adult. In turn, that adult would have a higher risk of obesity-related afflictions such as type 2 diabetes or cardiovascular disease...
At the ARS Children’s Nutrition Research Center at Baylor College of Medicine in Houston another researcher is studying the “epigenetic mechanism” link to obesity. The researchers studied a population of genetically similar laboratory mice known for their genetic tendency toward obesity. The findings suggest that “an epigenetic mechanism may act to increase the severity of obesity from one generation to the next.” This “transgenerational amplification of obesity” occurred in three successive generations of mice. Specifically, overweight dams gave birth to even-more-overweight offspring, the females of which gave birth to even heavier pups, and so on, through generation three.
Reported in the International Journal of Obesity, the study showed that the mothers’ obesity apparently induced changes in the expression of genes that control the formation of the pups’ body-weight-regulating mechanisms. That likely took place in the womb and perhaps in the weeks thereafter, setting the pups on the path to obesity.
At the ARS Children’s Nutrition Research Center at Baylor College of Medicine in Houston another researcher is studying the “epigenetic mechanism” link to obesity. The researchers studied a population of genetically similar laboratory mice known for their genetic tendency toward obesity. The findings suggest that “an epigenetic mechanism may act to increase the severity of obesity from one generation to the next.” This “transgenerational amplification of obesity” occurred in three successive generations of mice. Specifically, overweight dams gave birth to even-more-overweight offspring, the females of which gave birth to even heavier pups, and so on, through generation three.
Reported in the International Journal of Obesity, the study showed that the mothers’ obesity apparently induced changes in the expression of genes that control the formation of the pups’ body-weight-regulating mechanisms. That likely took place in the womb and perhaps in the weeks thereafter, setting the pups on the path to obesity.
Sunday, March 14, 2010
Scientists Identify Key Protein from Mitochondria in Energy Regulation
With obesity and obesity-related diseases epidemic in the developed world, a clear understanding of how metabolism is regulated is crucial. One of the key metabolic pathways involves the oxidation of fat. In the current edition of the journal Nature, scientists at the Gladstone Institute of Virology and Immunology report on a new mechanism that governs this pathway and in the process identified a novel potential therapeutic target for controlling fat metabolism.
The target is a protein from the mitochondria, or the "power plants" of every cell that are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
"Many mitochondrial proteins undergo a small chemical modification known as acetylation, which varies during feeding and fasting conditions," said Eric Verdin, MD, senior investigator and senior author of the study. "From our previous studies, we knew that the enzyme SIRT3 is involved in removing these modifications, and we speculated that SIRT3 might have a role in regulating metabolism and looked for how it might do this."
To study the enzyme's role in mice, the researchers used mice in which both copies of the gene had been deleted. Interestingly, mice that lost both copies of the SIRT3 gene appeared to be completely normal. However, the investigators then tested the mice under fasting conditions. During fasting, expression of SIRT3 was increased in the liver, an organ that helps maintain the body's energy balance. The livers of mice without SIRT3 had higher levels of fat and triglycerides than normal mice, because the mice could not burn fat...
The target is a protein from the mitochondria, or the "power plants" of every cell that are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.
"Many mitochondrial proteins undergo a small chemical modification known as acetylation, which varies during feeding and fasting conditions," said Eric Verdin, MD, senior investigator and senior author of the study. "From our previous studies, we knew that the enzyme SIRT3 is involved in removing these modifications, and we speculated that SIRT3 might have a role in regulating metabolism and looked for how it might do this."
To study the enzyme's role in mice, the researchers used mice in which both copies of the gene had been deleted. Interestingly, mice that lost both copies of the SIRT3 gene appeared to be completely normal. However, the investigators then tested the mice under fasting conditions. During fasting, expression of SIRT3 was increased in the liver, an organ that helps maintain the body's energy balance. The livers of mice without SIRT3 had higher levels of fat and triglycerides than normal mice, because the mice could not burn fat...
Saturday, March 13, 2010
Obesity as protection against metabolic syndrome, not its cause
The collection of symptoms that is the metabolic syndromeinsulin resistance, high cholesterol, fatty liver, and a greater risk for diabetes, heart disease, and strokeare all related to obesity, but, according to a review in the March 9th issue of the Cell Press publication Trends in Endocrinology and Metabolism, not in the way you probably think they are.
In fact, says Roger Unger of the University of Texas Southwestern at Dallas, obesity is the body's way of storing lipids where they belong, in fat tissue, in an effort to protect our other organs from lipids' toxic effects. It's when the surplus of calories coming in gets to be too much for our fat tissue to handle that those lipids wind up in other places they shouldn't be, and the cascade of symptoms known as metabolic syndrome sets in.
It comes down to simple facts that all of us know on some level or another: Americans since the 1950s eat too much high-calorie food loaded with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures") and, thanks to modern technology, we move far too little. Until that changes, Unger doesn't see any end to the growing epidemic of metabolic syndrome. Still, our metabolisms aren't broken; the pathways that squirrel fat away as an energy source for use in lean times are just completely overwhelmed. "We are pushing our homeostatic capability to the maximum," says Unger, who coined the term "lipotoxicity" in 1994. "Overnutrition used to be rarereserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."
Unger cites plenty of evidence in support of a protective role for obesity. Genetic manipulations in mice that increase or decrease fat formation have provided evidence that adipogenesis, meaning the generation of fat cells, delays other metabolic consequences of overeating. The reverse is also true, he writes. Obesity-resistant mice have in some cases been found to develop severe diabetes upon eating too much, as a result of lipid accumulation in tissues other than fat...
In fact, says Roger Unger of the University of Texas Southwestern at Dallas, obesity is the body's way of storing lipids where they belong, in fat tissue, in an effort to protect our other organs from lipids' toxic effects. It's when the surplus of calories coming in gets to be too much for our fat tissue to handle that those lipids wind up in other places they shouldn't be, and the cascade of symptoms known as metabolic syndrome sets in.
It comes down to simple facts that all of us know on some level or another: Americans since the 1950s eat too much high-calorie food loaded with carbs and fat (what Unger calls "potent adipogenic nutrient mixtures") and, thanks to modern technology, we move far too little. Until that changes, Unger doesn't see any end to the growing epidemic of metabolic syndrome. Still, our metabolisms aren't broken; the pathways that squirrel fat away as an energy source for use in lean times are just completely overwhelmed. "We are pushing our homeostatic capability to the maximum," says Unger, who coined the term "lipotoxicity" in 1994. "Overnutrition used to be rarereserved for those in the castle. Today, it's just the opposite. Bad calories are so cheap that anyone can afford to get overweight."
Unger cites plenty of evidence in support of a protective role for obesity. Genetic manipulations in mice that increase or decrease fat formation have provided evidence that adipogenesis, meaning the generation of fat cells, delays other metabolic consequences of overeating. The reverse is also true, he writes. Obesity-resistant mice have in some cases been found to develop severe diabetes upon eating too much, as a result of lipid accumulation in tissues other than fat...
Saturday, March 06, 2010
Mother's Milk Turns On The Heat
In newborn mice, at least, mother's milk appears to have some rather immediate and potentially far-reaching metabolic consequences. The milk intake kick-starts the liver to produce a molecule that then turns on heat-generating brown fat.
"A key phenomenon required after birth is to adapt the body to a lower environmental temperature with respect to that experienced when the fetus is inside the mother's womb," said Francesc Villarroya of the University of Barcelona. "We find that a key inducer of heat production in neonates is FGF21, released by the liver in response to the initiation of suckling."...
"A key phenomenon required after birth is to adapt the body to a lower environmental temperature with respect to that experienced when the fetus is inside the mother's womb," said Francesc Villarroya of the University of Barcelona. "We find that a key inducer of heat production in neonates is FGF21, released by the liver in response to the initiation of suckling."...
In Immune-Altered Mice Intestinal Bacteria Drive Obesity And Metabolic Disease
Increased appetite and insulin resistance can be transferred from one mouse to another via intestinal bacteria, according to research being published online this week by Sciencemagazine.
The finding strengthens the case that intestinal bacteria can contribute to human obesity and metabolic disease, since previous research has shown that intestinal bacterial populations differ between obese and lean humans.
The finding strengthens the case that intestinal bacteria can contribute to human obesity and metabolic disease, since previous research has shown that intestinal bacterial populations differ between obese and lean humans.
Thursday, March 04, 2010
Blood glucose-lowering hormone FGF21 also activates brown adipose tissue metabolism
The blood glucose-lowering hormone FGF21 is also an activator of brown adipose tissue metabolism, according to the study featured on the cover of Cell Metabolism and directed by the lecturer Francesc Villarroya of the UB's Department of Biochemistry and Molecular Biology (Faculty of Biology), the Institute of Biomedicine, and the Biomedical Research Networking Centre in Physiopathology of Obesity and Nutrition.
The study was carried out using newborn mice, and reveals possible new therapeutic targets for combating obesity using the fibroblast growth factor 21 (FGF21), which is secreted by the liver in response to fats in the diet. The team behind the research describe a novel action of FGF21 on brown adipose tissue, which governs energy expenditure and heat production in the body.
FGF21 is an antidiabetic and antiobesity agent that has been referred to in scientific literature since 2005", says Francesc Villarroya, an expert in the study of metabolism regulation models using genetically modified mice. He explains that, "Our study provides the first evidence that FGF21 causes thermogenesis in brown adipose tissue, that is, the burning of calories to release heat, dissipating large amounts of energy. Any agent that promotes and activates brown adipose tissue metabolism is, by definition, an antiobesity agent"...
The study was carried out using newborn mice, and reveals possible new therapeutic targets for combating obesity using the fibroblast growth factor 21 (FGF21), which is secreted by the liver in response to fats in the diet. The team behind the research describe a novel action of FGF21 on brown adipose tissue, which governs energy expenditure and heat production in the body.
FGF21 is an antidiabetic and antiobesity agent that has been referred to in scientific literature since 2005", says Francesc Villarroya, an expert in the study of metabolism regulation models using genetically modified mice. He explains that, "Our study provides the first evidence that FGF21 causes thermogenesis in brown adipose tissue, that is, the burning of calories to release heat, dissipating large amounts of energy. Any agent that promotes and activates brown adipose tissue metabolism is, by definition, an antiobesity agent"...
Transgenic Mice Could Solve The Obesity Epidemic
By tweaking an enzyme in mice, researchers expected to get rodents with low cholesterol, but fatty livers. Instead they found a switch which might be a weight loss miracle.
The researchers from the University of Alberta bred a mouse lacking a single enzyme that's associated with fat metabolism — triacylglycerol hydrolase (TGH). TGH is partly responsible for releasing triglycerides from the liver where they go on to form very low-density lipoproteins (VLDLs), which are considered "bad" cholesterol. The scientists thought that breeding a mouse deficient in TGH would have fewer VLDLs, and instead found the mice that not only had lower cholesterol, but also system wide metabolic improvement — seemingly without downside.
The researchers hypothesized that removing the TGH would mean the more fat would build up in the liver, as the mechanism by which the fat was released was missing. Instead of getting tiny rodent foie gras, the triglycerides were burned almost immediately rather than being stored, and the liver compensated by synthesizing less fat. The rodents ate more, but also expended more energy, and showed no change in body weight compared to their normal cousins...
The researchers from the University of Alberta bred a mouse lacking a single enzyme that's associated with fat metabolism — triacylglycerol hydrolase (TGH). TGH is partly responsible for releasing triglycerides from the liver where they go on to form very low-density lipoproteins (VLDLs), which are considered "bad" cholesterol. The scientists thought that breeding a mouse deficient in TGH would have fewer VLDLs, and instead found the mice that not only had lower cholesterol, but also system wide metabolic improvement — seemingly without downside.
The researchers hypothesized that removing the TGH would mean the more fat would build up in the liver, as the mechanism by which the fat was released was missing. Instead of getting tiny rodent foie gras, the triglycerides were burned almost immediately rather than being stored, and the liver compensated by synthesizing less fat. The rodents ate more, but also expended more energy, and showed no change in body weight compared to their normal cousins...
BPA And Obese Babies: Is There A Connection?
Drive-thru burgers and fries, movie theater popcorn with three days worth of fat and calories, video games, smart phones and TV, there are plenty of villains in the war against obesity. But all of the usual suspects don't explain the latest segment of the population with rising obesity rates – infants.
Research from Harvard University shows infant obesity has risen more than 70 percent since 1980. The numbers are staggering and confusing because babies eat only formula or breast milk and they've never been much into exercise.
"I get the question you know, 'how old is she?'. When I say 'six weeks', they say she looks like a three month old. She's definitely bigger," explained new mother Kelly Domina.
Domina is confident her 6-week old daughter will outgrow her baby fat but studies have shown big babies are at risk of being obese adults.
WHY ARE BABIES GETTING FAT?
Researchers believe a common household chemical may be to blame.
"Research has shown since 2001 that being exposed to BPA during development changes your body weight," explained Tufts University Scientist Dr. Laura Vandenberg.
BPA, or Bisphenol-A, is found in hundreds of consumer products. "Humans are most likely exposed to BPA through oral exposures," Vandenberg said. "BPA is used to line the inside of cans and that's thought to be a major exposure in adults."
Dr. Vandenberg and her colleagues have evidence that mice exposed to tiny amounts of BPA while in the womb gained more weight than mice that were not exposed. The animals didn't eat more and they got the same amount of exercise. "What actually happens is the fat cells have more fat in them so each cell is actually getting larger," Vandenberg said...
Research from Harvard University shows infant obesity has risen more than 70 percent since 1980. The numbers are staggering and confusing because babies eat only formula or breast milk and they've never been much into exercise.
"I get the question you know, 'how old is she?'. When I say 'six weeks', they say she looks like a three month old. She's definitely bigger," explained new mother Kelly Domina.
Domina is confident her 6-week old daughter will outgrow her baby fat but studies have shown big babies are at risk of being obese adults.
WHY ARE BABIES GETTING FAT?
Researchers believe a common household chemical may be to blame.
"Research has shown since 2001 that being exposed to BPA during development changes your body weight," explained Tufts University Scientist Dr. Laura Vandenberg.
BPA, or Bisphenol-A, is found in hundreds of consumer products. "Humans are most likely exposed to BPA through oral exposures," Vandenberg said. "BPA is used to line the inside of cans and that's thought to be a major exposure in adults."
Dr. Vandenberg and her colleagues have evidence that mice exposed to tiny amounts of BPA while in the womb gained more weight than mice that were not exposed. The animals didn't eat more and they got the same amount of exercise. "What actually happens is the fat cells have more fat in them so each cell is actually getting larger," Vandenberg said...
Soluble Rich-Fiber Foods Boost Immunity and Reduce Obesity, Study Reveals
A recent study at the University of Illinois has re-confirmed a very famous saying "An apple a day keeps doctor away" by concluding that soluble-fiber rich foods like oats, apples, and nuts not only help in lessening inflammation that leads to obesity, but also are capable of strengthening the immune system. It was found that the soluble fiber products produce interleukin-4, which is an anti-inflammatory protein.
Elaborating on the study, Gregory Freund, a Professor in the University of Illinois' College of Medicine said, "Soluble fiber changes the personality of immune cells, they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection".
In this study, laboratory mice were experimented as they were made to consume identical low-fat diets with soluble or insoluble fibers for six weeks. This study is expected to be published in the May 2010 issue of Brain, Behavior, and Immunity.
Elaborating on the study, Gregory Freund, a Professor in the University of Illinois' College of Medicine said, "Soluble fiber changes the personality of immune cells, they go from being pro-inflammatory, angry cells to anti-inflammatory, healing cells that help us recover faster from infection".
In this study, laboratory mice were experimented as they were made to consume identical low-fat diets with soluble or insoluble fibers for six weeks. This study is expected to be published in the May 2010 issue of Brain, Behavior, and Immunity.
With Just One Enzyme Missing, Mice Show 'Global' Metabolic Improvements
When researchers created mice lacking an enzyme that breaks down and releases stored triglycerides (more properly known as triacylglycerols or TGs), they expected to see animals with better lipid profiles. But according to a report in the March Cell Metabolism, a Cell Press publication, they got more than they bargained for. The triacylglycerol hydrolase (TGH)-deficient mice showed global metabolic benefits, with essentially no downside.
"It was a surprising and unexpected finding," said Richard Lehner of the University of Alberta. "With this gene deleted, not only was there a decline in very low-density lipoproteins in the whole mouse, it also affected metabolism in fat tissue. The insulin-secreting cells became smaller, suggesting that they didn't have to work as hard to secrete insulin, and the mice became more insulin sensitive." The animals ate more, but they also expended more energy and showed no change in body weight.
Very low-density lipoproteins (VLDLs) are a form of "bad" cholesterol, Lehner explained. TGH normally frees up triglycerides from their storage place in the liver, releasing them for assembly into VLDLs. Therefore, one might expect that loss of TGH would have ill effects on the liver, as triglycerides would build up there. Indeed, he says, similar experiments with other enzymes have shown such an effect.
"We didn't observe that here," Lehner said. "Instead of being stored in liver, triglycerides were directed for oxidation." In other words, they were burned. The liver also compensated by synthesizing less fat.
The studies demonstrate the potential of TGH as a therapeutic target for lowering blood lipid levels, with possible far-reaching beneficial side effects throughout the body. That may be especially worthy of note, given that drug companies already have a TGH blocker. In fact, Lehner's team earlier showed that the TGH-inhibiting drug can lower the secretion of VLDLs from liver cells. But it wasn't clear whether the drug was really acting only on TGH. The new findings add support to the notion that loss of TGH activity alone can have very significant and positive effects...
"It was a surprising and unexpected finding," said Richard Lehner of the University of Alberta. "With this gene deleted, not only was there a decline in very low-density lipoproteins in the whole mouse, it also affected metabolism in fat tissue. The insulin-secreting cells became smaller, suggesting that they didn't have to work as hard to secrete insulin, and the mice became more insulin sensitive." The animals ate more, but they also expended more energy and showed no change in body weight.
Very low-density lipoproteins (VLDLs) are a form of "bad" cholesterol, Lehner explained. TGH normally frees up triglycerides from their storage place in the liver, releasing them for assembly into VLDLs. Therefore, one might expect that loss of TGH would have ill effects on the liver, as triglycerides would build up there. Indeed, he says, similar experiments with other enzymes have shown such an effect.
"We didn't observe that here," Lehner said. "Instead of being stored in liver, triglycerides were directed for oxidation." In other words, they were burned. The liver also compensated by synthesizing less fat.
The studies demonstrate the potential of TGH as a therapeutic target for lowering blood lipid levels, with possible far-reaching beneficial side effects throughout the body. That may be especially worthy of note, given that drug companies already have a TGH blocker. In fact, Lehner's team earlier showed that the TGH-inhibiting drug can lower the secretion of VLDLs from liver cells. But it wasn't clear whether the drug was really acting only on TGH. The new findings add support to the notion that loss of TGH activity alone can have very significant and positive effects...
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