Unraveling a Cellular Mystery

...The cilia on some neurons in the brain contain receptors for melanin-concentrating hormone and possibly leptin—two vital parts of the body’s feeding-response system. These hormones mediate the sensation of being full or hungry to control feeding behavior; MCH induces feeding, while leptin represses the urge to eat. Mice with damaged cilia “can’t control their eating,” says Yoder. “They don’t understand when they’re full.” This fits with the clinical evidence in humans; obesity is a common symptom of many syndromes related to ciliary dysfunction...

Lose Sleep, Gain Weight: Another Piece of the Obesity Puzzle

It's 11 P.M., and you sit in front of a glowing computer screen, writing e-mails and eating a sandwich. You'll work until after midnight, when you'll fall asleep in front of the light and blare of a TV before rising again at 6 A.M. What's wrong with this picture? Because of modern conveniences and pressures, many of us keep our bodies exposed to light, food, and activity at times when our organs and cells expect dark, quiet, and sleep.

In epidemiologic studies, shorter sleep has been correlated with incidence of obesity, hypertension, and other metabolic disorders. Experimental sleep studies find a similar connection. Increasingly, studies of the possible mechanisms behind these associations suggest that lack of sleep is part of a bigger problem with the 24/7 lifestyle many people today lead. Increasingly, scientists are finding that many physiologic activities related to metabolism don't happen continuously but oscillate on a regular schedule. Studies in mice as well as humans suggest that when our internal clock is disrupted, it may throw off many bodily functions, especially metabolism...

Corcept Therapeutics Initiates a Phase 1 Study of Its Lead Selective Cortisol Receptor (GR-II) Antagonist -- CORT 108297

...A microdosing study of CORT 108297 in healthy humans was completed in March 2008, and demonstrated that the compound is well absorbed, has good bioavailability and has a half-life that appears compatible with once-a-day oral dosing. In 2009 we announced results from preclinical studies of CORT 108297 which demonstrated a statistically significant impact on multiple metabolic markers. Specifically, studies of CORT 108297 combined with olanzapine, the active ingredient in Eli Lilly's antipsychotic medication Zyprexa, administered to rats over a 3-week period demonstrated a dose dependent mitigation of weight gain across doses ranging from 2 to 120mg/kg. CORT 108297 also showed statistically significant benefit in preventing weight gain in a preclinical obesity model in which mice were given a high fat diet and a high sucrose drink ("fast food" diet) for four weeks, as well as in a model of modulation of insulin sensitivity...

Auburn Prof. Finds Possible Link Between Alzheimer’s and Obesity

An Auburn professor says she has discovered a genetic link between obesity and Alzheimer’s disease.

Marie Wooten, Associate Dean for research and a biology professor, says that if a certain protein molecule, P62, is absent from the brain in mice, they became obese and more susceptive to Alzheimer’s...

Gut bacteria can cause obesity

The authors base their viewpoint on tens of experimental studies carried out mostly on laboratory animals. These studies apparently show that the intestines of mice which suffer from obesity contain more bacteria types which efficiently convert indigestible food into manageable fatty acids. When researchers transplanted the gut flora of obese mice into mice without such gut flora, the fat percentage increased significantly in these so-called germ-free mice. It is suspected that the gut flora (known as gut microbiota) of these obese mice also affects hormones involved in fat storage.

Humans suffering from obesity also have such efficient gut bacteria, the authors surmise. They would therefore derive more energy from food and become fat easier. Various studies also point to this view, although the results are not always conclusive. Professor Willem de Vos, one of the authors of the publication, says: 'The study of gut bacteria in humans is rather complex. Every human being has a unique composition of microbiota, which makes research difficult. We want to use this review article as a first step into a territory which is abandoned by and large. Research into the relationship between microbiota and obesity in humans can only begin afterwards.'

Bilberry Seems to Act Against Blood Sugar

Bilberry extract helps control blood sugar levels in mice, researchers have found.

Bilberry and other brightly colored foods such as blueberries, purple grapes, cherries and cranberries contain anthocyanins, which are thought to reduce blood sugar, improve insulin sensitivity and reduce obesity in laboratory mice.

To study these effects further, Japanese researchers used mice genetically predisposed to develop diabetes. The mice were fed either a diet containing bilberry extract (27 grams per kilogram) or their normal diet for five weeks.

The study authors found that bilberry extract lowered blood glucose and increased insulin sensitivity in the mice. It did this by activating AMP-activated protein kinase (AMPK) in white adipose (fat) tissue, skeletal muscle and the liver, the researchers explained. AMPK stimulates fat breakdown in liver and muscle, and modulates insulin secretion by the pancreas.

Scientists find protein culprit for obesity

Researchers have discovered a protein that leads to obesity. Previous studies reveal that one protein - p62 - produced obesity in mice when scientists studied how obesity occurs in the absence of p62. Now scientists have discovered a protein that pairs with p62 and is the real culprit that promotes fat cell growth and leads to obesity.

The new findings show that the ERK protein works in conjunction with p62 to make fat cells in the body that in turn leads to obesity, insulin resistance, and eventually diabetes and other obesity related problems.

In earlier research, Jorge Moscat, PhD, chair of UC’s cancer and cell biology department at the University of Cincinnati found that mice who lack p62 became fat and used less energy, becoming insulin resistant in adulthood, compared to mice who ate the same diet and expended the same amount of energy - an important note for individuals who despite exercise and diet cannot lose weight.

Development Of Dietary Formula That Maintains Youthful Function Into Old Age

Researchers at McMaster University have developed a cocktail of ingredients that forestalls major aspects of the aging process.

The findings are published in the current issue of Experimental Biology and Medicine.

"As we all eventually learn, ageing diminishes our mind, fades our perception of the world and compromises our physical capacity," says David Rollo, associate professor of biology at McMaster. "Declining physical activity - think of grandparents versus toddlers - is one of the most reliable expressions of ageing and is also a good indicator of obesity and general mortality risk."

The study found that a complex dietary supplement powerfully offsets this key symptom of ageing in old mice by increasing the activity of the cellular furnaces that supply energy - or mitochondria - and by reducing emissions from these furnaces - or free radicals - that are thought to be the basic cause of ageing itself.

Most of the primary causes of human mortality and decline are strongly correlated with age and free-radical processes, including heart disease, stroke, Type II diabetes, many cancers, neurodegenerative diseases, and inflammatory and autoimmune conditions. Successful intervention into the ageing process could consequently prevent or forestall all of these.

Using bagel bits soaked in the supplement to ensure consistent and accurate dosing, the formula maintained youthful levels of locomotor activity into old age whereas old mice that were not given the supplement showed a 50 per cent loss in daily movement, a similar dramatic loss in the activity of the cellular furnaces that make our energy, and declines in brain signaling chemicals relevant to locomotion. This builds on the team's findings that the supplement extends longevity, prevents cognitive declines, and protects mice from radiation.

Ingredients consists of items that were purchased in local stores selling vitamin and health supplements for people, including vitamins B1, C, D, E, acetylsalicylic acid, beta carotene, folic acid, garlic, ginger root, ginkgo biloba, ginseng, green tea extract, magnesium, melatonin, potassium, cod liver oil, and flax seed oil. Multiple ingredients were combined based on their ability to offset five mechanisms involved in ageing.

Cutting Off the Blood Supply to Fat Cells Could Become a New Obesity Therapy

White fat is the "bad" gut fat associated with obesity and enlarged abdomens. When a pound of new white fat forms in the body, it requires a full mile of new blood vessels to nourish and sustain it. That's because white fat is much like a tumor in requiring a steady blood supply. To build the new blood vessels, it depends on a process called angiogenesis.

Using the tumor analogy, researchers at the University of Cincinnati's Metabolic Diseases Institute wondered what would happen if they attacked white fat by cutting off its blood supply and starving it. To find the answer, they used a proapoptotic (literally, "leading to death") peptide* targeted at the blood vessels in white fat. They found that without its blood supply, the fat "starved" and began to disappear.

The researchers treated both obese and lean rats and mice with the proapoptotic peptide for periods of four or 27 days, monitoring their food intake and energy levels. Some of the rodents, already obese, had been on high-fat diets to make them overweight. Others, not obese, were placed on high-fat diets for purposes of the study. Another group of non-obese mice and rats were on low-fat diets.

The researchers found that the peptide totally reversed the diet-induced obesity of the already obese mice, and it reduced the weight of the other rodents that had been recently placed on high-fat diets. The peptide had no effect on the mice and rats on the low-fat diet. The researchers also found that although the peptide lowered the appetite and food intake among the obese and high-fat-diet rodents, it did not affect their energy levels. Despite consuming less food, the mice and rats did not experience a drop-off in their expenditures of energy...

Maternal obesity predisposes baby to Alzheimer's

...The study was based on rats.

"We hope these data will eventually lead to treatments for obesity-associated problems, by the identification of novel targets within the immune system," said Staci D. Bilbo, Ph.D., co-author of the study, from the Department of Psychology and Neuroscience at Duke University in Durham, N.C. "Our hope is also that these data will lead people to consider the consequences of their dietary intakes not only for their own health, but also for their children;s health, and potentially even their grand children's health."

To reach the conclusion, Bilbo and colleagues placed rats on one of three diets (low-fat, high-saturated fat, and high-trans fat) four weeks prior to mating and throughout pregnancy and lactation. The high-fat diets rendered the mice clinically obese. Researchers analyzed the brains of the newborn pups after challenge by inflammatory stimuli.

Offspring born to mothers on the high-fat diets showed increased immune cell activation and release of injurious products (cytokines). This overshoot was already apparent on the day after birth. When the scientists continued to analyze the pup brains through their juvenile and adult years, and even after the rats were put on healthy low-fat diets, this hyper-response to inflammation remained dramatically increased compared to rats born to normal-weight mothers.

"If there ever was a maternal hex, obesity might be it," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal , "and as it turns out, even after the weight comes off, the biggest loser isn’t a mother, but her child."

Molecular 'Firing Squad' in Mice Triggered by Overeating Destroys Metabolism

Overeating in mice triggers a molecule once considered to be only involved in detecting and fighting viruses to also destroy normal metabolism, leading to insulin resistance and setting the stage for diabetes. The new study, led by researchers at the Harvard School of Public Health (HSPH), specifically links together the immune system and metabolism, a pairing increasingly suspected in diseases that include -- in addition to diabetes -- heart disease, fatty liver, cancer, and stroke.

Understanding how to regulate the molecule through targeted drugs or nutrients could eventually change the way these diseases are prevented and treated in humans.

Is There a Right and Wrong Time to Eat?

It’s very possible that our ever-increasing waistlines are affected not only by what we put into our mouth, but when we partake in meals. A recent study endeavored to prove that choosing the right time to eat could make a difference in the amount of weight we gain.

After noticing the tendency of shift workers to be overweight, researchers from Northwestern University investigated whether eating at times that conflict with the body’s natural circadian rhythms could be contributing to weight gain. Two groups of lab mice were fed an identical high-fat diet and experienced the same amount of exercise. The only difference between the two was the feeding time: one group was fed at night, which is the normal feeding time for mice since they are nocturnal, while the other group was fed during the day, their normal resting time.

The mice eating at the correct time had a 20 percent weight gain after six weeks, while the second group experienced a 48 percent gain in weight, as well as an increase of 8 percent more body fat. Study co-author Fred Turek, director of Northwestern’s Center for Sleep and Circadian Biology, said the findings seem to show there really is a wrong time to eat. “How or why a person gains weight is very complicated, but it clearly is not just calories in and calories out,” he said in a statement. “Better timing of meals, which would require a change in behavior, could be a critical element in slowing the ever-increasing incidence of obesity.”

Study finds drinking tea may slim your waistline

It all started in 2737 B.C. when the second emperor of China, Shen Nung, discovered tea after tea leaves blew into his cup of hot water. And now it’s the world’s second most consumed beverage, after water. Just ask the tea drinkers gathering at TahCha tea house in Atlanta, who sip on a variety of teas, for a variety of reasons.

Tea has been long used by the Chinese for medicinal and health purposes, and now there’s a study that claims the hot beverage could trim your waistline.

A recent study shows that men who drink more than two cups of tea a day have thinner waistlines than men who drink coffee or nothing at all. However, for ladies the same doesn't hold true.

The study, which came out at the First International Congress on Abdominal Obesity, looks at the relationship between coffee and tea drinking and stomach obesity. The exact connection between tea and a thinner waistline isn’t exactly understood. Researchers say the role between tea drinking and a trim waistline in men and women deserves more study.

When it comes to coffee and tea drinking, the use of sugar vs. artificial sweeteners seems to play a role in abdominal obesity. And the findings might surprise you. For men, the use of sugar in tea was associated with a nearly 1-inch smaller waist measurement, but the use of artificial sweeteners was linked to a nearly 2-inch larger waistline. Among women, the use of milk in tea was associated with a two-thirds-of-an-inch smaller waistline. But women who used artificial sweeteners had an average of nearly an inch larger waistline.

Green tea has long been associated with weight loss. In tests, among mice with an obesity gene, those that ate food with green tea extract gained less weight and less fat. There was less sign of fatty liver disease in the mice with the obesity gene that ate green tea extract. And the mice had lower cholesterol and triglyceride levels.

Blocking Enzyme in Mice Reduces Fat

Blocking a single enzyme leads to increased energy expenditure and loss of body fat -- at least in mice, researchers said.

Mice treated with a compound that blocks the so-called Fyn kinase expended 14% more energy than animals treated with an inert compound, according to Claire Bastie, PhD, and colleagues at Albert Einstein College of Medicine in New York City.

They also displayed a significant weight loss within 12 hours of receiving the compound, compared with animals given the inert substance, Bastie and colleagues reported in the Feb. 3 issue of Cell Metabolism.

"This is a new mechanism to help the body to burn extra energy," Bastie said in a statement.

The Fyn kinase has previously been linked to energy use: animals with the enzyme blocked burn more fatty acids and are leaner than their normal littermates, Bastie and colleagues noted.

Those animals also had increased insulin sensitivity, the researchers said, but the absence of the enzyme did not block the normal anabolic processes of protein synthesis and muscle growth during the feeding cycle.

The findings suggested that drugs blocking the enzyme might have a significant effect on energy balance and weight, they theorized.

Fat-Burning Chemical Points to New Weight-Loss Drug

American scientists say they may have found a new way to trick the body into burning more fat.

Mice that were given a chemical that blocks the function of an enzyme called Fyn kinase burned more fatty acids and expended more energy, which made them leaner. This and other metabolic improvements, including increased insulin sensitivity, were because of higher levels of the "master energy switch" AMPK in the rodents' fat and muscle tissue.

The findings suggest that Fyn kinase may offer a target for a new kind of weight-loss drug, said the researchers at the Albert Einstein College of Medicine and Neuroscience. The study appears in the Feb. 3 issue of the journal Cell Metabolism.

"When there is an imbalance between what we eat and what we burn," the result is obesity, team leader Claire Bastie said in a news release from the journal. "And the problem of obesity is not going away. This is a new mechanism to help the body burn extra energy."

Stress Hormone's Startling Powers

A hormone that can wreak havoc with the body by setting off harmful effects of stress may have a far more positive use: in a new way to treat diabetes.

The hormone, known as corticotropin-releasing factor, or CRF, has been implicated in anxiety, obesity, addiction and even Alzheimer's disease. The brain and other organs make CRF. It triggers a cascade of chemicals that ultimately produce cortisol and adrenaline and activate the body's "fight or flight" response. Under chronic stress, cortisol breaks down muscle, suppresses the immune system and raises the risk of high blood pressure.

But recently, researchers have showed that CRF increases both insulin secretion and production of the cells that make insulin in the pancreas, known as beta cells. Diabetes, which affects nearly 24 million Americans, involves the body's inability to properly use insulin to convert sugar into usable energy. The findings, which support a hunch that others in the field have had, point to a possible pathway for treatment of diabetes.

"The machinery that allows the cell to respond to the hormone has been found," says Wylie Vale, a professor of molecular neurobiology at the La Jolla, Calif., Salk Institute for Biological Studies, who discovered the structure of CRF in 1981. "We are exploring how this machinery is controlled under conditions such as diabetes and obesity. What we really want to do is understand the system." The research of Dr. Vale and his colleagues was reported in a December paper published in the Proceedings of the National Academy of Sciences.

With Type 1 diabetes, formerly known as juvenile diabetes, the body doesn't produce enough insulin. This happens because the immune system attacks and kills beta cells. These patients are treated with insulin injections.

The most common form of diabetes, associated with obesity, is Type 2. Here, the body doesn't produce enough insulin and the cells from insulin-responsive tissues like muscle are unable to efficiently use the insulin that is produced. The beta cells go into overdrive to try to produce insulin but become overworked and ultimately stop functioning, according to Patricia Kilian, head of the beta-cell-regeneration program at the Juvenile Diabetes Research Foundation, which partially funded the study.