...Working with mice, the researchers reported in the journal Cell that paternal diet can influence the production of genes that direct metabolism in first-generation offspring, and particularly influence how they're able to process cholesterol.
The study is one of a number done recently that look at how the environment and lifestyle of a previous generation can influence the genetics of the next, going beyond traits that are known to be passed from generation to generation through mutations in DNA.
"Knowing what your parents were doing before you were conceived is turning out to be important in determining what disease factors you may be carrying," said Dr. Oliver Rando, an associate professor at the University of Massachusetts and lead investigator for the study.
"Our findings suggest there are many ways that parents can tell their children things."
Rando and his colleagues fed two groups of male mice different diets — one a low-protein diet, the other standard chow; while all the females in the test got the standard diet before breeding started.
They found that the offspring of the male mice fed the low-protein diet showed a marked increase in genes responsible for blood fats and cholesterol breakdown compared to those sired by mice fed the standard diet.
Although the study involved mice, the research actually has its roots in several human observational studies that suggested there was a paternal and even grand-paternal effect from diet on the risks for diabetes, obesity and heart disease...
Sunday, March 06, 2011
Scientists Discover Genetic Switch That Increases Muscle Blood Supply
Many people suffer from a devastating condition known as critical limb ischemia (CLI) that can lead to muscle wasting and even amputation. The disease is linked to the blockage of blood flow to the skeletal muscle and current treatment options include rehabilitative exercise and surgical bypass of blood vessels. New preclinical research suggests there may be a way to restore blood supply in skeletal muscle without traditional intervention.
Scientists at The University of Texas Health Science Center at Houston (UTHealth) and the Salk Institute for Biological Studies announced in the March 2 print issue of the journal Cell Metabolism that they have identified a genetic switch that can increase the number of blood vessels in the skeletal muscle of non-exercising mice.
Skeletal muscle is composed of two types of fibers: slow twitch fibers that inherently have a dense supply of blood vessels and fast twitch fibers that have fewer blood vessels. The researchers used a gene switch known as estrogen-related receptor gamma (ERR gamma) that when activated in fast twitch fibers of mice by genetic engineering, converts these fibers into slow twitch fibers.
"This consequently resulted in a striking increase in muscle blood supply as measured by imaging and angiography," said Vihang Narkar, Ph.D., lead investigator and assistant professor of molecular medicine at the UTHealth Medical School. "These genetically-transformed muscles also acquire other characteristics of slow muscles, such as improved metabolic capacity and fatigue resistance that can be additionally beneficial in resolving muscle vascular disease."
Narkar, whose UTHealth laboratory is in the Center for Diabetes and Obesity Research at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, said, "The identification of the estrogen-related receptor gamma vascular switch will open potential therapeutic avenues for treating CLI and other cardiovascular diseases linked to defective blood supply."
Colin Barker, M.D., assistant professor of cardiology at the UTHealth Medical School, said new research is needed to help people with peripheral artery disease, particularly those with the most severe form - critical limb ischemia. "Poor circulation in the legs can lead to muscle wasting, infections, severe pain, and amputation," he said. "Dr. Narkar's work potentially has many useful applications. It is very much in the translational medicine arena."
"Understanding the gene network that specifies high vascular supply to muscle gives us a new and very powerful tool to promote improved muscle performance and the promise of fitness, especially for those who cannot work out," says Ronald M. Evans, Ph.D., senior author, Howard Hughes Medical Institute Investigator and professor in the Salk Institute's Gene Expression Laboratory. "This is good news for people with heart disease, frailty, peripheral vascular disease, and more generally those who have a variety of medical problems where exercise could be helpful but is not possible to achieve."
In 2010, an estimated 2.8 to 3.5 million U.S. citizens suffered from critical limb ischemia, according to a report by THE SAGE GROUP, an independent research and consulting company specializing in peripheral artery disease. CLI risk factors include diabetes, obesity and smoking...
Scientists at The University of Texas Health Science Center at Houston (UTHealth) and the Salk Institute for Biological Studies announced in the March 2 print issue of the journal Cell Metabolism that they have identified a genetic switch that can increase the number of blood vessels in the skeletal muscle of non-exercising mice.
Skeletal muscle is composed of two types of fibers: slow twitch fibers that inherently have a dense supply of blood vessels and fast twitch fibers that have fewer blood vessels. The researchers used a gene switch known as estrogen-related receptor gamma (ERR gamma) that when activated in fast twitch fibers of mice by genetic engineering, converts these fibers into slow twitch fibers.
"This consequently resulted in a striking increase in muscle blood supply as measured by imaging and angiography," said Vihang Narkar, Ph.D., lead investigator and assistant professor of molecular medicine at the UTHealth Medical School. "These genetically-transformed muscles also acquire other characteristics of slow muscles, such as improved metabolic capacity and fatigue resistance that can be additionally beneficial in resolving muscle vascular disease."
Narkar, whose UTHealth laboratory is in the Center for Diabetes and Obesity Research at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, said, "The identification of the estrogen-related receptor gamma vascular switch will open potential therapeutic avenues for treating CLI and other cardiovascular diseases linked to defective blood supply."
Colin Barker, M.D., assistant professor of cardiology at the UTHealth Medical School, said new research is needed to help people with peripheral artery disease, particularly those with the most severe form - critical limb ischemia. "Poor circulation in the legs can lead to muscle wasting, infections, severe pain, and amputation," he said. "Dr. Narkar's work potentially has many useful applications. It is very much in the translational medicine arena."
"Understanding the gene network that specifies high vascular supply to muscle gives us a new and very powerful tool to promote improved muscle performance and the promise of fitness, especially for those who cannot work out," says Ronald M. Evans, Ph.D., senior author, Howard Hughes Medical Institute Investigator and professor in the Salk Institute's Gene Expression Laboratory. "This is good news for people with heart disease, frailty, peripheral vascular disease, and more generally those who have a variety of medical problems where exercise could be helpful but is not possible to achieve."
In 2010, an estimated 2.8 to 3.5 million U.S. citizens suffered from critical limb ischemia, according to a report by THE SAGE GROUP, an independent research and consulting company specializing in peripheral artery disease. CLI risk factors include diabetes, obesity and smoking...
Sunday, February 27, 2011
Diet and exercise restore immune function in obesity
Boston University scientists say that moderate daily exercise and dietary control might reverse immune dysfunctions found in people with obesity.
Overeating and a sedentary lifestyle are well-known risk factors for obesity, which is linked to hypertension, heart disease, diabetes, gum disease, certain cancers, and asthma.
Research has suggested that a change in immune function is a predecessor to all these diseases and researchers at Boston University Henry M. Goldman School of Dental Medicine (GSDM) have previously shown that obesity causes immune defects that make it hard to fight infection.
Until now, little was known about how diet and exercise affects immunity in obese people.
Researchers worked with diet-induced obese mice in four groups:
• lean mice on a standard chow diet
• obese mice on a high fat diet
• obese mice on a high fat diet on a moderate exercise plan for four weeks, and
• obese, high fat diet mice given moderate exercise and a four-week standard chow diet
Moderate daily exercise and dietary control dramatically restored immune function. Obese mice saw damaged cytokines—signaling molecules that help immune cells talk to each other—repaired and an improved ability to fight gum disease as measured by bone loss.
“The study underscores the necessity to correct two important factors in obesity—diet and exercise—to improve markers of immune dysfunction and bone loss,” says senior author Dr. Salomon Amar. “The correction of one factor only may not lead to any tangible changes.”...
Overeating and a sedentary lifestyle are well-known risk factors for obesity, which is linked to hypertension, heart disease, diabetes, gum disease, certain cancers, and asthma.
Research has suggested that a change in immune function is a predecessor to all these diseases and researchers at Boston University Henry M. Goldman School of Dental Medicine (GSDM) have previously shown that obesity causes immune defects that make it hard to fight infection.
Until now, little was known about how diet and exercise affects immunity in obese people.
Researchers worked with diet-induced obese mice in four groups:
• lean mice on a standard chow diet
• obese mice on a high fat diet
• obese mice on a high fat diet on a moderate exercise plan for four weeks, and
• obese, high fat diet mice given moderate exercise and a four-week standard chow diet
Moderate daily exercise and dietary control dramatically restored immune function. Obese mice saw damaged cytokines—signaling molecules that help immune cells talk to each other—repaired and an improved ability to fight gum disease as measured by bone loss.
“The study underscores the necessity to correct two important factors in obesity—diet and exercise—to improve markers of immune dysfunction and bone loss,” says senior author Dr. Salomon Amar. “The correction of one factor only may not lead to any tangible changes.”...
Treadmill the fountain of youth: study
Exercising on a treadmill for 45 minutes, three times a week, warded off the effects of premature aging in lab mice, a McMaster University study shows.
The researchers hope that when people see the dramatic difference between sedentary mice and those with the treadmill routine, it’ll give them an extra push to get off the couch.
Anything that motivates people to exercise is beneficial because it’s good for human health, decreasing rates of obesity and Type 2 diabetes while increasing longevity, said Dr. Mark Tarnopolsky of McMaster’s Michael G. DeGroote School of Medicine...
The researchers hope that when people see the dramatic difference between sedentary mice and those with the treadmill routine, it’ll give them an extra push to get off the couch.
Anything that motivates people to exercise is beneficial because it’s good for human health, decreasing rates of obesity and Type 2 diabetes while increasing longevity, said Dr. Mark Tarnopolsky of McMaster’s Michael G. DeGroote School of Medicine...
New research suggests that obesity and diabetes are a downside of human evolution
...In this study, which is the first to examine the effect of a human-specific CMAH genetic mutation in obesity-related metabolism and diabetes, Kim and colleagues show that the loss of CMAH's function contributes to the failure of the insulin-producing pancreatic beta cells in overweight humans, which is known to be a key factor in the development of type 2 diabetes. This gene encodes for an enzyme present in all mammalian species except for humans and adds a single oxygen atom to sialic acids, which are sugars that coat the cell surface.
To make their discovery, the researchers used two groups of mice. The first group had the same mutant CMAH gene found in humans. These mice demonstrated that the CMAH enzyme was inactive and could not produce a sialic acid type called NeuSGc at the cell surface. The second group had a normal CMAH gene. When exposed to a high fat diet, both sets of mice developed insulin resistance as a result of their obesity. Pancreatic beta cell failure, however, occurred only in the CMAH mutant mice that lacked NeuSGc, resulting in a decreased insulin production, which then further impaired blood glucose level control. This discovery may enhance scientific understanding of why humans may be particularly prone to develop type 2 diabetes. Results may also suggest that conventional animal models may not accurately mirror the human situation.
"The diabetes discovery is an important advance in its own right. It tells us a lot about what goes wrong in diabetes, and where to aim with new treatments," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but its implications for human evolution are even greater. If this enzyme is unique to humans, it must also have given us a survival advantage over earlier species. Now the challenge is to find the function of CMAH in defending us against microbes or environmental stress or both. This evolutionary science explains how we can win some and lose some, to keep our species ahead of the extinction curve."
To make their discovery, the researchers used two groups of mice. The first group had the same mutant CMAH gene found in humans. These mice demonstrated that the CMAH enzyme was inactive and could not produce a sialic acid type called NeuSGc at the cell surface. The second group had a normal CMAH gene. When exposed to a high fat diet, both sets of mice developed insulin resistance as a result of their obesity. Pancreatic beta cell failure, however, occurred only in the CMAH mutant mice that lacked NeuSGc, resulting in a decreased insulin production, which then further impaired blood glucose level control. This discovery may enhance scientific understanding of why humans may be particularly prone to develop type 2 diabetes. Results may also suggest that conventional animal models may not accurately mirror the human situation.
"The diabetes discovery is an important advance in its own right. It tells us a lot about what goes wrong in diabetes, and where to aim with new treatments," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal, "but its implications for human evolution are even greater. If this enzyme is unique to humans, it must also have given us a survival advantage over earlier species. Now the challenge is to find the function of CMAH in defending us against microbes or environmental stress or both. This evolutionary science explains how we can win some and lose some, to keep our species ahead of the extinction curve."
Monday, February 14, 2011
Mapping obesity circuitry in brain
In the battle of the bulge, one important battalion is a set of brain cells expressing the melanocortin-4 receptor (MC4R). Via signals from the fat-derived hormone leptin, these neurons regulate feeding behavior and fat metabolism in an attempt to regulate body weight. But how leptin influences and acts on this brain circuitry is not fully understood.
Using mice with fluorescently-tagged MC4R, Masoud Ghamari-Langroudi, Roger Cone and colleagues analyzed how the activity of MC4R neurons of the paraventricular nucleus of the hypothalamus (PVN) are regulated by leptin and by metabolic state (i.e., fasting).
They report in the Jan. 4 Proceedings of the National Academy of Sciences that fasting increases firing of these neurons and that leptin administration returns the firing to normal levels. They also show that contrary to the conventional view that leptin indirectly regulates PVN neuron activity, it can also inhibit the activity of PVN neurons directly. Such details of the brain circuitry underlying energy balance could provide important clues to understanding – and combating – obesity.
Using mice with fluorescently-tagged MC4R, Masoud Ghamari-Langroudi, Roger Cone and colleagues analyzed how the activity of MC4R neurons of the paraventricular nucleus of the hypothalamus (PVN) are regulated by leptin and by metabolic state (i.e., fasting).
They report in the Jan. 4 Proceedings of the National Academy of Sciences that fasting increases firing of these neurons and that leptin administration returns the firing to normal levels. They also show that contrary to the conventional view that leptin indirectly regulates PVN neuron activity, it can also inhibit the activity of PVN neurons directly. Such details of the brain circuitry underlying energy balance could provide important clues to understanding – and combating – obesity.
Diet drug makers seeking new strategies
...The search for new drug pathways that alter the body’s metabolism, and the way calories are burned and stored as fat, gained momentum in 2009 when researchers from the University of Michigan, Vanderbilt University and Fudan University in Shanghai published a paper in the journal Cell exploring the relationship between inflammation in the fat tissue of mice and obesity and diabetes.
They focused on a protein that activates immune-system white blood cells that cause fat cells to swell.
In regular mice that were fed a high-calorie diet, the protein activated white blood cells, causing fat cells to swell. The mice gained weight and became insulin-resistant, a condition known as Type 2 diabetes.
Another group of mice were genetically engineered to lack the protein. Those animals were also overfed, but they didn’t gain weight. Instead, their bodies consumed more oxygen and produced greater amounts of another type of protein that generates body heat by burning fat tissue.
As an added benefit, the engineered mice didn’t develop diabetes.
They focused on a protein that activates immune-system white blood cells that cause fat cells to swell.
In regular mice that were fed a high-calorie diet, the protein activated white blood cells, causing fat cells to swell. The mice gained weight and became insulin-resistant, a condition known as Type 2 diabetes.
Another group of mice were genetically engineered to lack the protein. Those animals were also overfed, but they didn’t gain weight. Instead, their bodies consumed more oxygen and produced greater amounts of another type of protein that generates body heat by burning fat tissue.
As an added benefit, the engineered mice didn’t develop diabetes.
Mayo Clinic researcher's memory study leads to surprising obesity finding
Their mission was to solve a small but nagging mystery of Alzheimer's disease: How would the brain's ability to store information be affected if they "turned off" the obscure protein LRP1?
But Guojun Bu and his fellow researchers were in for a surprise. As they expected, mice whose brains had been wiped of the LRP1 gene showed Alzheimer's-like memory problems. But they also started to put on weight - fast.
The mice were lethargic. They were on their way to becoming diabetic. And they didn't seem to know when to stop eating.
In other words, they were a lot like the more than 72 million Americans who are obese...
But Guojun Bu and his fellow researchers were in for a surprise. As they expected, mice whose brains had been wiped of the LRP1 gene showed Alzheimer's-like memory problems. But they also started to put on weight - fast.
The mice were lethargic. They were on their way to becoming diabetic. And they didn't seem to know when to stop eating.
In other words, they were a lot like the more than 72 million Americans who are obese...
Sunday, February 06, 2011
Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle
Divergently selected Lean and Fat mouse lines represent unique models for a polygenic form of resistance and susceptibility to obesity development. Previous research on these lines focused mainly on obesity-susceptible factors in the Fat line.
This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes.
Results: Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line...
This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes.
Results: Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line...
Biochemistry analyses mouse resistance to obesity
Mechanisms that allow mice to resist developing obesity have been analysed using gel filtration chromatography by a team of French and Slovenian biochemistry and veterinary scientists...
Sunday, January 30, 2011
New molecular player responsible for regulation of appetite and metabolism
A study by researchers at Mayo Clinic's campus in Florida and Washington University School of Medicine adds a new twist to the body of evidence suggesting human obesity is due in part to genetic factors. While studying hormone receptors in laboratory mice, neuroscientists identified a new molecular player responsible for the regulation of appetite and metabolism...
Study suggests designer probiotics could help cut obesity
Targeted probiotics could affect the physiology of human fat cells and potentially prevent or help treat conditions such as obesity, according to new Irish research.
Recently published in Microbiology, the study from scientists at Teagasc (the Irish Agriculture and Food Development Authority), University College Cork and the Alimentary Pharmabiotic Centre examined whether a lactobacillus strain with CLA (conjugated linoleic acid) influenced fat tissue composition in mice.
Previous research from Racine et al. (2010) and Thom et al. (2001) has linked fatty acid t10, c12 CLA consumption with decreased body fat in humans, while other studies suggest that this type of fatty acid inhibits colon cancer cell growth.
Probiotics assists CLA metabolism
In this study, scientists transferred an enzyme-encoding gene from skin bacterium P.acnes to Lactobacillus paracasei and induced it to produce CLA t10, c12, which fed to mice resulted in a fourfold increase of CLA in mouse fat tissue composition (against a second probiotic control strain) showing that live bacteria intake affects metabolism at remote body sites...
Warmer Houses May Increase Obesity
...Unlike mice fed a typical low-fat laboratory diet, adjusting their intake to the ambient temperature, mice fed high-fat diets do not decrease their food intake at higher temperatures and gain weight.
"These human and animal experimental models suggest that while intake is somewhat suppressed at higher temperatures, this is unlikely to fully compensate for the reduced energy expenditure of a warm environment particularly where highly palatable foods are available," Johnson and colleagues observed.
This research argues in favor of a causal link between increased time spent in thermal comfort and weight gain in the population, they said...
"These human and animal experimental models suggest that while intake is somewhat suppressed at higher temperatures, this is unlikely to fully compensate for the reduced energy expenditure of a warm environment particularly where highly palatable foods are available," Johnson and colleagues observed.
This research argues in favor of a causal link between increased time spent in thermal comfort and weight gain in the population, they said...
Obesity Drug Moving to Clinical Trials Following Success in Mice, Dogs, and Women
A successful trial on a small number of obese women in Australia demonstrated that those treated with intravenous Zafgen-433 lost an average of approximately two pounds per week. In addition to the weight loss, the women experienced a decline in hunger and reductions in triglycerides and low-density lipoprotein (LDL) cholesterol levels, all with no serious, treatment-related adverse events. Now, following the positive results of this initial double-blind, placebo-controlled, proof-of-concept trial, Zafgen expects to have a subcutaneous form of the drug ready by the end of summer which will be used for the next phase of clinical trials (for both men and women) expected to begin sometime later in 2011. Ultimately, though, the company plans to create a conventional, oral form of the medication...
Zafgen's innovative approach to reversing obesity targets adipose tissue (fat cells) because, unlike the traditional view of obesity that fat accumulation is a "passive result of other factors," Zafgen views adipose tissue "as playing an active role in the disease," a view that represents a "fundamentally new paradigm" in how obesity is regarded and potentially treated. Indeed, obese people release fat from their adipose tissue at a slower rate than the non-obese, and they convert it to ketone bodies – a form that is usable as fuel for muscles – at a slower rate. (Much of this process encompasses the metabolic syndrome and insulin resistance that doctors described when discussing obesity as a risk for type 2 diabetes.) Zafgen-433 acts on adipose tissue by inhibiting an enzyme called methionine aminopeptidase 2, or MetAP2, an enzyme that is associated with the body's tendency for preserving its stores of fat. When this enzyme is inhibited by the drug, it allows the body to metabolize fatty acids at a more normalized rate as the body re-establishes its balance, leading to a substantial loss of body weight in overweight individuals. This was true for the overfed mice (pictured above), for overweight dogs, and for the initial trial of obese women in Australia. Adipose tissue samples from the treated mice revealed that their fat cells actually shrank...
Zafgen's innovative approach to reversing obesity targets adipose tissue (fat cells) because, unlike the traditional view of obesity that fat accumulation is a "passive result of other factors," Zafgen views adipose tissue "as playing an active role in the disease," a view that represents a "fundamentally new paradigm" in how obesity is regarded and potentially treated. Indeed, obese people release fat from their adipose tissue at a slower rate than the non-obese, and they convert it to ketone bodies – a form that is usable as fuel for muscles – at a slower rate. (Much of this process encompasses the metabolic syndrome and insulin resistance that doctors described when discussing obesity as a risk for type 2 diabetes.) Zafgen-433 acts on adipose tissue by inhibiting an enzyme called methionine aminopeptidase 2, or MetAP2, an enzyme that is associated with the body's tendency for preserving its stores of fat. When this enzyme is inhibited by the drug, it allows the body to metabolize fatty acids at a more normalized rate as the body re-establishes its balance, leading to a substantial loss of body weight in overweight individuals. This was true for the overfed mice (pictured above), for overweight dogs, and for the initial trial of obese women in Australia. Adipose tissue samples from the treated mice revealed that their fat cells actually shrank...
Sunday, January 23, 2011
Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur
Backgound: Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition.
To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (uCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice.
Methods: Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and uCT measurements.
Results: The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR), with increased epididymal fat pad mass and impaired insulin sensitivity.
These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia.
Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure.
Conclusions: The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth...
To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (uCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice.
Methods: Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and uCT measurements.
Results: The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR), with increased epididymal fat pad mass and impaired insulin sensitivity.
These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia.
Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure.
Conclusions: The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth...
The Microbes In Our Gut Regulate Genes That Control Obesity And Inflammation
If you are looking to lose weight in the coming year, you may need help from an unexpected place: the bacteria in your gut. That's because scientists have discovered that the bacteria living in your intestines may play a far more significant role in weight loss and gastrointestinal problems than ever imagined. In a new research report published online in The FASEB Journal (http://www.fasebj.org), researchers show that a deficiency of Toll-like receptor 2 (Tlr2) - used by mammals (including humans) to recognize resident microbes in the intestines - leads to changes in gut bacteria that resemble those of lean animals and humans. This discovery builds on previous research demonstrating that a deficiency of TLR2 protects against obesity, while at the same time promoting gastrointestinal problems like excessive inflammation. It also shows that genes controlling TLR2 expression play a very important role in one's gastrointestinal health and weight management.
"Our work highlights the remarkable capacity for an orchestrated reprogramming of the intestinal inflammatory network to overcome significant genetic challenges in the mammalian bowel," said Richard Kellermayer, Ph.D., a researcher involved in the work from the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston. "The appropriate exploitation of this remarkable capacity may provide means for the prevention and optimized treatment of common metabolic (such as obesity and diabetes) and gastrointestinal disorders."
To make this discovery, Kellermayer and colleagues studied normal mice and mice deficient in TLR2 using the large intestinal lining of these mice. They compared the TLR2-deficient ones to the normal group, as well as the bacteria, the epigenome (more specifically DNA methylation, a molecular change in the DNA associated with decreased gene expression), and the gene expression of the animals. The researchers found that the absence of TLR2 leads to microbial changes in the gut that resemble lean animals and humans, as well as immunologic changes similar to those observed in ulcerative colitis...
"Our work highlights the remarkable capacity for an orchestrated reprogramming of the intestinal inflammatory network to overcome significant genetic challenges in the mammalian bowel," said Richard Kellermayer, Ph.D., a researcher involved in the work from the Section of Pediatric Gastroenterology, Hepatology and Nutrition at Baylor College of Medicine in Houston. "The appropriate exploitation of this remarkable capacity may provide means for the prevention and optimized treatment of common metabolic (such as obesity and diabetes) and gastrointestinal disorders."
To make this discovery, Kellermayer and colleagues studied normal mice and mice deficient in TLR2 using the large intestinal lining of these mice. They compared the TLR2-deficient ones to the normal group, as well as the bacteria, the epigenome (more specifically DNA methylation, a molecular change in the DNA associated with decreased gene expression), and the gene expression of the animals. The researchers found that the absence of TLR2 leads to microbial changes in the gut that resemble lean animals and humans, as well as immunologic changes similar to those observed in ulcerative colitis...
Sunday, January 16, 2011
A magic calorie ride
Bob, an office supervisor in Toronto, considers himself an addict. But the substance he’s prone to abusing isn’t drugs or alcohol—it’s food. “I would gorge on Raisinets, pizza, anything that I could get in quantity,” says Bob, 60, who asked that his last name not be used. He ran up a $4,000 Visa bill, almost all of it on food. Eating as a stress release, “I averaged about 15,000 calories a day.” He weighed 336 lb. at his heaviest. “I’m no scientist, but I think it’s an addiction,” he says. “When I read about how a drug addict behaves, my response is the same to food.”
The term “food addiction” is controversial, but recent studies have shown that high-calorie foods engage the same regions of the brain as drugs like heroin and cocaine. Over time, scientists say, a high-fat diet can impair the brain’s pleasure centres like those drugs do, encouraging ever-larger binges and making it harder to quit. Remarkably, a mother’s diet might even hard-wire her baby for obesity later on in life. “It’s too early to call it food addiction,” says Teresa Reyes of the University of Pennsylvania School of Medicine, who studies how the brain adapts to changes in diet. “But there is absolutely increasing evidence showing that the brain responds to high-sucrose, high-fat diets in a very similar way that it responds to drugs of abuse.”
At the Society for Neuroscience’s annual conference in November, Reyes presented her latest work: mice that were fed a high-fat diet for a long period of time, she found, showed changes in parts of their brains associated with pleasure and reward. Just like cocaine or heroin, unhealthy foods seem to trigger the brain’s pleasure centres, eventually desensitizing them. It becomes a vicious cycle. “To reach the same level of reward, the person needs to eat more rewarding food,” Reyes says. “It’s very similar to what happens in chronic drug abuse.” (This data is now under review before publication.)...
The term “food addiction” is controversial, but recent studies have shown that high-calorie foods engage the same regions of the brain as drugs like heroin and cocaine. Over time, scientists say, a high-fat diet can impair the brain’s pleasure centres like those drugs do, encouraging ever-larger binges and making it harder to quit. Remarkably, a mother’s diet might even hard-wire her baby for obesity later on in life. “It’s too early to call it food addiction,” says Teresa Reyes of the University of Pennsylvania School of Medicine, who studies how the brain adapts to changes in diet. “But there is absolutely increasing evidence showing that the brain responds to high-sucrose, high-fat diets in a very similar way that it responds to drugs of abuse.”
At the Society for Neuroscience’s annual conference in November, Reyes presented her latest work: mice that were fed a high-fat diet for a long period of time, she found, showed changes in parts of their brains associated with pleasure and reward. Just like cocaine or heroin, unhealthy foods seem to trigger the brain’s pleasure centres, eventually desensitizing them. It becomes a vicious cycle. “To reach the same level of reward, the person needs to eat more rewarding food,” Reyes says. “It’s very similar to what happens in chronic drug abuse.” (This data is now under review before publication.)...
Bacteria in the gut help control obesity and inflammation
Researchers at Baylor College of Medicine in Houston have discovered that the bacteria living in the intestines may play a far more significant role in weight loss and gastrointestinal problems than ever imagined.
They show that a deficiency of Toll-like receptor 2 (Tlr2)-used by mammals (including humans) to recognize resident microbes in the intestines-leads to changes in gut bacteria that resemble those of lean animals and humans.
This discovery builds on previous research demonstrating that a deficiency of TLR2 protects against obesity, while at the same time promoting gastrointestinal problems like excessive inflammation.
It also shows that genes controlling TLR2 expression play a very important role in one's gastrointestinal health and weight management.
The team studied normal mice and mice deficient in TLR2 using the large intestinal lining of these mice. They compared the TLR2-deficient ones to the normal group, as well as the bacteria, the epigenome and the gene expression of the animals.
The researchers found that the absence of TLR2 leads to microbial changes in the gut that resemble lean animals and humans, as well as immunologic changes similar to those observed in ulcerative colitis...
They show that a deficiency of Toll-like receptor 2 (Tlr2)-used by mammals (including humans) to recognize resident microbes in the intestines-leads to changes in gut bacteria that resemble those of lean animals and humans.
This discovery builds on previous research demonstrating that a deficiency of TLR2 protects against obesity, while at the same time promoting gastrointestinal problems like excessive inflammation.
It also shows that genes controlling TLR2 expression play a very important role in one's gastrointestinal health and weight management.
The team studied normal mice and mice deficient in TLR2 using the large intestinal lining of these mice. They compared the TLR2-deficient ones to the normal group, as well as the bacteria, the epigenome and the gene expression of the animals.
The researchers found that the absence of TLR2 leads to microbial changes in the gut that resemble lean animals and humans, as well as immunologic changes similar to those observed in ulcerative colitis...
New findings may lead to a novel treatment for obesity
Scientists have added a new twist to the body of evidence suggesting human obesity is due in part to genetic factors.
While studying hormone receptors in laboratory mice, researchers at Mayo Clinic's campus in Florida and Washington University School of Medicine identified a new molecular player responsible for the regulation of appetite and metabolism.
The authors report that mice engineered not to express the lipoprotein receptor LRP1, in the brain's hypothalamus, began to eat uncontrollably, growing obese as well as lethargic. They found that LRP1, a major transporter of lipids and proteins into brain cells, is a "co-receptor" with the leptin receptor - meaning that both the leptin and LRP1 receptors need to work together to transmit leptin signals.
Leptin decides whether fat should be stored or used, resulting in lethargy or energy. When working properly, the hormone, which is made when body cells take in fat from food, travels to the brain to tamp down appetite...
While studying hormone receptors in laboratory mice, researchers at Mayo Clinic's campus in Florida and Washington University School of Medicine identified a new molecular player responsible for the regulation of appetite and metabolism.
The authors report that mice engineered not to express the lipoprotein receptor LRP1, in the brain's hypothalamus, began to eat uncontrollably, growing obese as well as lethargic. They found that LRP1, a major transporter of lipids and proteins into brain cells, is a "co-receptor" with the leptin receptor - meaning that both the leptin and LRP1 receptors need to work together to transmit leptin signals.
Leptin decides whether fat should be stored or used, resulting in lethargy or energy. When working properly, the hormone, which is made when body cells take in fat from food, travels to the brain to tamp down appetite...
Sunday, January 09, 2011
Thanks, Dad
Fathers, as well as mothers, can pass on a propensity to obesity if they themselves have been starved
THAT a gestating mother’s environment can have a permanent effect on the physiology of her offspring is well established. The children of Dutch women who were pregnant during the “Hunger Winter” of 1944, for example, suffer much higher rates of obesity, diabetes and cardiovascular disease than those born a year or two earlier. Similar observations in other famines, together with experiments on rodents, suggest this is an accidental consequence of an evolutionary adaptation to food scarcity. The offspring of starving mothers, anticipating hard times during their own future lives, adjust their metabolisms to hoard calories. If the hard times then go away, the result is a tendency to put on weight, with the unpleasant consequences that entails.
Part of this adaptation is a response by the embryo to the nutrition it receives through the placenta. In some cases, though, the unfertilised ovum itself is believed to be affected. Its DNA is reprogrammed, the theory goes, by a process called cytosine methylation. This switches genes on and off in a way that is maintained when DNA replicates during the process of cell division—and can thus be passed down the generations. It is, moreover, a process that could apply equally to the sperm of putative fathers who were starved around the time of mating.
There are hints that it does. In particular, a recent paper by Sheau-Fang Ng of the University of New South Wales showed that gene activity in the pancreases of mice sired by fat fathers is abnormal. That is significant because the pancreas makes insulin, which regulates blood sugar. Abnormal insulin levels cause diabetes...
THAT a gestating mother’s environment can have a permanent effect on the physiology of her offspring is well established. The children of Dutch women who were pregnant during the “Hunger Winter” of 1944, for example, suffer much higher rates of obesity, diabetes and cardiovascular disease than those born a year or two earlier. Similar observations in other famines, together with experiments on rodents, suggest this is an accidental consequence of an evolutionary adaptation to food scarcity. The offspring of starving mothers, anticipating hard times during their own future lives, adjust their metabolisms to hoard calories. If the hard times then go away, the result is a tendency to put on weight, with the unpleasant consequences that entails.
Part of this adaptation is a response by the embryo to the nutrition it receives through the placenta. In some cases, though, the unfertilised ovum itself is believed to be affected. Its DNA is reprogrammed, the theory goes, by a process called cytosine methylation. This switches genes on and off in a way that is maintained when DNA replicates during the process of cell division—and can thus be passed down the generations. It is, moreover, a process that could apply equally to the sperm of putative fathers who were starved around the time of mating.
There are hints that it does. In particular, a recent paper by Sheau-Fang Ng of the University of New South Wales showed that gene activity in the pancreases of mice sired by fat fathers is abnormal. That is significant because the pancreas makes insulin, which regulates blood sugar. Abnormal insulin levels cause diabetes...
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