Monday, November 30, 2009

Western Diets Turn on Fat Genes: Energy-Dense Foods May Activate Genes That Ultimately Make Us Obese

"Those extra helpings of gravy and dessert at the holiday table are even less of a help to your waistline than previously thought. According to a new research report recently appearing online in The FASEB Journal, a diet that is high in fat and in sugar actually switches on genes that ultimately cause our bodies to store too much fat.

This means these foods hit you with a double-whammy as the already difficult task of converting high-fat and high-sugar foods to energy is made even harder because these foods also turn our bodies into "supersized fat-storing" machines.

In the research report, scientists show that foods high in fat and sugar stimulate a known opioid receptor, called the kappa opioid receptor, which plays a role in fat metabolism. When this receptor is stimulated, it causes our bodies to hold on to far more fat than our bodies would do otherwise.

According to Traci Ann Czyzyk-Morgan, one of the researchers involved in the work, 'the data presented here support the hypothesis that overactivation of kappa opioid receptors contribute to the development of obesity specifically during prolonged consumption of high-fat, calorically dense diets.'

To make this discovery, Czyzyk-Morgan and her colleagues conducted tests in two groups of mice. One group had the kappa opioid receptor genetically deactivated ('knocked out') and the other group was normal. Both groups were given a high fat, high sucrose, energy dense diet for 16 weeks. While the control group of mice gained significant weight and fat mass on this diet, the mice with the deactivated receptor remained lean. In addition to having reduced fat stores, the mice with the deactivated receptor also showed a reduced ability to store incoming nutrients.

Although more work is necessary to examine what the exact effects would be in humans..."

Thursday, November 26, 2009

When You Eat Is As Vital As What You Eat

"An India-American researcher has said that when you eat may be as vital as what you eat.

Experiments in mice showed that the daily waxing and waning of thousands of genes in the liver - the body's metabolic clearing house - is generally controlled by intake of food and not by the body's circadian clock as conservative wisdom believes...

The studies by Salk researchers could clarify why shift workers are oddly prone to diabetes, high cholesterol levels and obesity."

Blocked receptor may prevent weight gain

"Drug-based weight loss therapies try to stop the brain from sending hunger signals to the body. These therapies tend to be fairly ineffective. Now researchers have discovered that if certain receptors are blocked in mice, they may be resistant to gaining fat...

They found that if they blocked NPY receptors (Y1) in the peripheral tissues of mice fed with high calorie diets, those mice were resistant to gaining body weight and fat."

Molecule that makes obese people develop diabetes discovered

"European researchers have discovered a molecule that they believe could play a role in causing diabetes in obese people.

They found that obese people have large amounts of the chemokine molecule CXCL5, produced by certain cells in fatty tissue.

They then discovered that an experimental treatment aimed at inhibiting the action of CXCL5 could help to protect obese mice from developing type-2 diabetes."

New Study Shows CoQ10 May Prevent Obesity-Related Health Problems

"Obesity is an ever growing problem with numerous health issues associated with it. One of those issues is called fatty liver. Fatty liver, also called steatosis, is the collection of excessive amounts of triglycerides and other fats inside liver cells. When fatty liver is left untreated, it can contribute to many other illnesses. But, a recent animal study indicates that coenzyme Q10 (CoQ10) might hamper the development of fatty liver that is related to obesity.

Animal Study Suggests Positive Affects of CoQ10 on Fatty Liver

Biochemical Pharmacology published findings related to mice that were fed a high fructose high fat diet. The mice that had their diet enhanced with CoQ10 showed decreased levels of inflammatory and metabolic stress markers in their livers when compared to those that were strictly provided the high fructose high fat diet. The supplement did not seem to have any effect on obesity levels or the levels of oxidised fat in other tissues."

Friday, November 20, 2009

Paper Chase: Discovery of fat gene in mice may help humans

"A 15-page research report suggests Stuart Little may one day want to toss his calorie counter. Mice apparently have a fat gene, that when deactivated, according to a study released this fall by the University of Michigan Life Sciences Institute, keeps rodents on high-fat diets thin...

Why it matters

Obesity and Type II diabetes are on the rise in America, and are a growing problem in children and adolescents. If a gene similarly linked to obesity is identified in humans, it could lead to the development of drugs to treat and prevent excessive weight gain and health problems associated with it.

The same research team is searching for molecules that may be able to block the gene's activity.

Which offers the possibility of guiltless consumption of bon-bons."

Thursday, November 12, 2009

Yoghurt story 'hard to swallow'

"A headline in today’s Daily Mail stated: 'Yoghurt drinks could beat bugs that pile the weight on.' It said scientists have shown that 'bugs that live in our stomachs could be causing us to get fat.' The newspaper said the research could lead to probiotic yoghurts that can combat weight gain.

The newspaper’s claim about probiotic yoghurts is misleading. In fact, the study examined the effect of a change in diet on gut flora (micro organisms found in the gut) and weight in mice...

A Western diet caused mice to gain weight and changed the microbes in their gut. Transplanting the gut flora from these mice to healthy mice led to significant weight gain compared with mice that received gut flora from mice on a non-Western diet, even though there was no increase in food consumption...

The study did not examine the effects of yoghurt or other probiotics on weight, as some news reports imply. Nor does it suggest that a probiotic yoghurt will soon be available that can aid weight loss. This extrapolation of the results is likely to have been based on the finding that a Western diet alters the microbial constituents of the gut. Researchers found that when the mice’s diet was changed from a low-fat diet to a Western-style high-fat, high-sugar diet, the component bacteria in their gut changed quickly and considerably. Stating that a probiotic yoghurt could 'combat weight gain', (sic) and including a picture of a normal yoghurt drink next to the article, could mislead people."

Connections Between Circadian And Metabolic Systems Described

"A paper by University of Notre Dame biologist Giles Duffield and a team of researchers offers new insights into a gene that plays a key role in modulating the body's Circadian system and may also simultaneously modulate its metabolic system. The relationship between circadian and metabolic systems the researchers describe could have important implications for understanding the higher incidence of cardiovascular disease, obesity and diabetes among shift workers...

Not only did the knockout mice have abnormal time-of-day specific changes in the pattern of gene activity, they also exhibited profound physiological changes. The mutant mice were lean, had smaller quantities of white fat stored in their abdomen and far less fat droplets in the liver itself."

Is your gut bacteria making you fat? Common microorganisms may contribute to obesity

"There are billions of microorganisms in the human gut, and according to a recent study, they may be triggers of obesity.

A study published in Science Transnational Medicine indicates that when these common microorganisms encounter a Westernized diet high in carbohydrates and sugar, the microbial environment shifts and results in weight gain.

According to HealthDay, researchers at the Center for Genome Sciences at Washington University School of Medicine in St. Louis observed the microbial changes in the guts of mice. They started with mice who, by way of genetic manipulation, had no bacteria in the gut. They then transplanted human microbes into the mice.

'When we switched these humanized animals [from a low-fat] to a junk-food diet, high in fat with lots of simple sugars, the structure of the microbial community changed dramatically and very rapidly,' study senior author Dr. Jeffrey I. Gordon told HealthDay Reporter. 'These mice also became obese on Western diets.'

Because the human body is made up of 10 times more microbial cells than human cells, researchers believe it’s vital to know how the food we eat affects microbial activity.

While it would be easy to blame the mice’s weight gain on the high-fat diet, scientists also transplanted microorganisms in several mice and fed them a low-fat diet, but yielded the same results...

Perhaps the most vital conclusion out of this study, however, is that there is a direct correlation between dietary habits and microbial activity that may lead to new treatments for obesity."

Tuesday, November 10, 2009

Brown fat cells provide hope for obesity research

"Not all fat cells mean weight gain.

National researchers in cell biology have identified proteins that turn normal skin cells into brown fat cells, which use energy to generate heat.

'Energy only gets burned when your heart beats or your muscles walk up a flight of stairs or when you breathe,' said Clay Semenkovich, chief of the division of endocrinology, metabolism and lipid research at the Washington University School of Medicine.

Brown fat cells do not store energy. They burn it without carrying out a function, such as beating the heart or walking, Semenkovich said.

Until recently, scientists believed that only animals and human babies had brown fat cells. But researchers discovered brown fat cells in adults when PET scans showed higher rates of glucose metabolism in patients who had been waiting in cold waiting rooms at their doctors’ offices.

Brown fat evolved to help people and animals in cold environments stay warm, Semenkovich said.

“People were freezing in the waiting rooms, and they were actually turning on brown fat,” he said.

The presence of brown fat cells in human adults carries implications for obesity research.

'People who are overweight have much less active brown fat,' Semenkovich said.

Researchers at Harvard engineered skin cells from mice and humans to become brown fat. This technology requires further research, though, before scientists can test it on humans.

'There’s always a disadvantage to tricking the body into doing things that it probably should not do,' Semenkovich said.

With brown fat, that disadvantage stems from the heat that the cells release. The excess heat could lead to dangerous and possibly deadly fevers in humans."

Brain link tips the scales

"BALWYN professor Michael Cowley has some welcome news for those struggling to lose weight - willpower alone is not the answer.

Prof Cowley has been awarded the 2009 Science Minister’s Prize for Life Scientist of the Year for his research into understanding metabolism and obesity.

The Monash University Department of Physiology professor has spent the past 10 years researching the complex issue of how people’s brains control their metabolism.

'There are good metabolic reasons why we struggle to lose weight,' Prof Cowley said.'“It’s not just about willpower. For some of us, compulsive food consumption mirrors drug addiction.'

Working with mice and monkeys, Prof Cowley identified neurons in the brain that responded to leptin, a hormone that helps regulate body weight.

He found leptin activated neurons that suppressed weight, and inhibited those increasing it."

Thursday, November 05, 2009

Bionovo Announces Third Quarter 2009 Highlights and Financial Results

"-- The Company presented the results of a study on the effects of two plant-derived, tissue-selective estrogen receptor alpha (ERa) modulators (TSERaM) on menopausal obesity at the 20th Annual Meeting of the North American Menopause Society. In this study, plant-derived TSERaMs,like estrogens, were shown to reduce body fat in mice, but while estrogens also caused cell proliferation in the mammary gland and uterus, the plant-derived TSERaMs did not elicit these potentially cancer-causing side effects. These results suggest that the development of botanically-derived, tissue-selective ERa modulators could result in a safer alternative for the treatment of menopausal weight gain, a condition that can lead to the development of metabolic syndrome, a combination of risk factors for cardiovascular disease and diabetes."

Tuesday, November 03, 2009

‘Slimming gene’ that regulates body fat identified

"Scientists at the University of Bonn have identified a gene in fruit flies that controls the metabolism of fat.

The researchers called the gene ’schlank’ (German for ’slim’).

According to them, the discovery could help in developing new medicines to fight obesity as mammals also carry a group of genes that are structurally very similar to ’schlank’.

The larvae in which this gene is defective have been found to lose their entire fat reserves.

According to Professor Michael Hoch from the University of Bonn, ‘in extreme cases the defect can even lead to death.’

The study showed that the gene contains the instructions of what is known as ceramide synthase. Ceramides serve as raw materials for the gauzy membranes that enclose all of the cells in the body.

Moreover, schlank also has a regulatory function. It promotes lipid synthesis and at the same time inhibits the mobilisation of fat from the fat reserves.

This gene is striking similar to Lass genes from mice that partially compensate for the defect schlank gene in mutant flies."

How saturated fatty acids 'anger' the immune system (and how to stop them)

"Researchers have new evidence to explain how saturated fatty acids, which soar in those who are obese, can lead the immune system to respond in ways that add up to chronic, low-grade inflammation. The new results could lead to treatments designed to curb that inflammatory state, and the insulin resistance and type 2 diabetes that come with it.

One key, according to the report in the November Cell Metabolism, a Cell Press publication, is an immune receptor (called Toll-like receptor 4 or Tlr4) at the surface of blood cells, including a particularly 'angry' class of macrophages known to pump out toxic molecules and spur inflammation. It now appears that fatty acids may in essence 'hijack' those immune cells via Tlr4...

The researchers showed in another Cell Metabolism report last year that a 'genetic trick' designed to kill off the offending macrophages, which are distinguished by a CD11c marker, could reverse insulin resistance in obese mice...

They say that drugs aimed at Tlr4 have already been developed, and the idea that those drugs may hold promise in fighting insulin resistance and type 2 diabetes is one Olefsky's team is now exploring in detail in the mice."

UNMC Study Yields Clues to Cell Metabolism, Obesity

"A University of Nebraska Medical Center research study could provide new clues on cell metabolism including how energy is regulated and used. The findings, published as the cover story in the latest issue of Cell Metabolism, show that mice are obese and insulin resistant when they lack a gene that interacts with, and controls, enzymes that regulate a cell’s energy level."

Monday, November 02, 2009

A scramble to harness the metabolic power of brown fat

"Americans spend millions each year searching for the right diet or exercise program -- all in an effort to shed some fat. But there's one type of fat that most would probably like to hold on to: brown fat.

Instead of storing excess energy from food in lumps and bumps throughout the body -- like its well-known sister, white fat -- brown fat helps burn incoming calories.

Because its primary purpose is temperature regulation, brown fat cells are jam-packed with mitochondria, the powerhouses of cells. This mitochondria-heavy design is well-suited to use high quantities of sugar, the body's fuel, and then release that energy in the form of heat.

This mechanism enables small and hibernating mammals, who can't shiver, to stay warm in cold temperatures. And it enables newborn humans, who have yet to develop layers of white fat, to stay warm after exiting the stable confines of the womb.

Until recently, only these two types of creatures were thought to even have brown fat.

Now researchers have found that adults don't, in fact, lose all of their brown fat to the creeping ubiquitousness of white fat; with that finding, they've launched a scramble to discover how the substance's fat-burning abilities could be harnessed for weight loss.

If brown fat is unleashed, it could potentially "tickle" the metabolism enough to make weight loss easier and more manageable, said Sven Enerback, a researcher at the University of Gothenburg in Sweden and one of the scientists who discovered that brown fat persists in adults. As is, once a person reduces his or her starting weight, the body begins to compensate for the loss by getting better gas mileage -- that is, burning fewer calories.

Enerback calculates that inserting only 50 to 100 grams of activated brown fat into a person could significantly increase their energy metabolism and eliminate 10 pounds of white fat a year.

However, these gains in metabolic rate can be achieved only if the brown fat is active. "When heat is not needed, the burner is off -- so we need to find good ways to activate it safely," he said.

The role of cold

Researchers are exploring various avenues through which to do this. It's possible cold temperatures may play a role.

Already they've learned in experiments exposing a variety of people to cold temperatures that healthy people tend to have more active brown fat than their less healthy, older or more overweight counterparts, said Dr. Aaron Cypess of the Joslin Diabetes Center in Boston. But researchers are not sure whether the brown fat helped lead to better health or whether people in better health have more brown fat. Further investigation will need to determine whether brown fat actually plays a protective role against obesity.

"First, we need to know the significance of brown fat function in human adults -- we can look at how to increase brown fat -- but first we need to understand it more," said Wouter van Marken Lichtenbelt, a professor of physiology at Maastricht University in the Netherlands and a co-discoverer of brown fat in adults.

Recently, a team of researchers led by Dr. Bruce Spiegelman, a professor of cell biology at the Dana-Farber Cancer Institute in Boston, was able to increase brown fat stores in mice by turning immature muscle cells into brown fat cells, then transplanting these cells into adult mice."

Scientists discover gene that controls the metabolism of fat

"Scientists at the University of Bonn have discovered a previously unknown fruit fly gene that controls the metabolism of fat. Larvae in which this gene is defective lose their entire fat reserves. Therefore the researchers called the gene 'schlank' (German for 'slim'). Mammals carry a group of genes that are structurally very similar to 'schlank'. They possibly take on a similar function in the energy metabolism. The scientists therefore have hopes in new medicines with which obesity could be fought. Their research bas been published in 'The EMBO Journal' (doi: 10.1038/emboj.2009.305)...

Mouse gene saves fly larvae

There is a chance that this is not only the case in fruit flies. Humans also produce ceramide synthases however not just one as Drosophila does but rather as many as six different ones. For this purpose humans rely on a group of genes so-called Lass genes. Ceramide synthases are extremely important for animals. Mutations in the corresponding genes lead to severe metabolic disorders and to malfunctions of organ systems. That is why our Lass genes look surprisingly similar to the schlank gene of fruit flies.

This resemblance is so striking that Lass genes from mice can partially compensate for the defect schlank gene in mutant flies. 'We introduced a mouse Lass gene in mutant Drosophila larvae,' Michael Hoch says. 'Normally the larvae died immediately after hatching. Thanks to the Lass gene they resumed building up body fat and survived until the next development stage.'"

The Chemical Cause of Fat

"There is a new and growing scientific explanation for obesityand obesity-related disorders, like cardiovascular disease, hypertension and type 2 diabetes, which does not involve living in a couch-potato culture and stuffing yourself with more calories than you can burn.
Dr. Bruce Blumberg, Professor for the Department of Pharmaceutical Sciences at UC Irvine, and his colleagues have determined thatobesogens, especially those that are environmental contaminants, are a possible explanation for the worldwide epidemic...

Connie Chow, a fourth-year biological sciences major, and Tiffany Kieu, a fourth-year developmental and cell biology major, are the only undergraduates currently working on the project. Their work is in submission to be reviewed for publication in a journal...

Blumberg and his colleagues have done a previous study showing that pregnant mice treated with TBT will have pup that become fatter when they grow up. Kieu assisted her post-doctoral supervisor, Severine Kirchner, with examining how prenatal exposure to TBT in the womb can later effect the development and function of adipose tissue in young mice. In this research, Kieu contributed most extensively to the RNA analysis"

Mice and Men

"The price tag on a mouse bred at Jackson Laboratory in Bar Harbor runs anywhere from $11 to $300. The lower fee buys a basic, all-purpose mouse, fit for a variety of scientific experiments, while a bit more gets a custom rodent with a disease of the customer’s choice. The mice can be ordered online, in bulk, and packed up in temperature-controlled tractor trailers for delivery within days. While supplies last, take 25% off selected products. Just add shipping and handling.

All this may sound rather commercial for a nonprofit, world-renowned genetics research institution. But selling mice has been part of Jackson Lab’s mission ever since the 1929 stock market crash threatened its founding 80 years ago. Today, the lab houses and distributes more than 4,000 different strains of mice — ideal as a research model for their genetic similarity to humans — and is recognized worldwide for its diverse, reliable stock. It is not the only place to buy laboratory mice, but its rodents are indispensable to scientists across the globe researching how and why we get sick...

The research driving personalized medicine is happening both in-house at Jackson Lab and at the pharmaceutical companies and biotechs the lab supplies with its mice. The lab employs 218 researchers working to understand and better treat diseases including cancer, osteoporosis, AIDS, obesity and glaucoma. Last year, the lab distributed 2.5 million mice — which are genetically pure through inbreeding — to 16,000 investigators in 60 countries. Many of them couldn’t do similar testing otherwise, Woychik says. 'There are major pharmaceutical companies whose R&D efforts are dependent on the resources that we create here. We’re doing experiments in mice that will make it safer to bring a drug into clinical trials.'...

Jackson Lab also provides mice that can accept human tissue, allowing researchers to test the efficacy of new drugs on as human-like a subject as possible. Hospitals provide the lab with human tumors that can be inserted into the mice, furthering research into cancer drugs, as well treatments for illnesses including as obesity and diabetes. 'You’re one step closer to really studying the human disease in life, not in a petri dish,' Hewett says."