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...
Saturday, June 19, 2010
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.
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