Apple Peel Compound Boosts Brown Fat, Reduces Obesity in Mice

Obesity and its associated problems such as diabetes and fatty liver disease are increasingly common global health concerns. A new study by University of Iowa researchers shows that a natural substance found in apple peel can partially protect mice from obesity and some of its harmful effects.

The findings suggest that the substance known as ursolic acid reduces obesity and its associated health problems by increasing the amount of muscle and brown fat, two tissues recognized for their calorie-burning properties.

The study, which was published June 20 in the journal PLoS ONE, was led by Christopher Adams, M.D., Ph.D., UI associate professor of internal medicine and a Faculty Scholar at the Fraternal Order of Eagles Diabetes Research Center at the UI.

"From previous work, we knew that ursolic acid increases muscle mass and strength in healthy mice, which is important because it might suggest a potential therapy for muscle wasting," Adams says. "In this study, we tested ursolic acid in mice on a high-fat diet -- a mouse model of obesity and metabolic syndrome. Once again, ursolic acid increased skeletal muscle. Interestingly, it also reduced obesity, pre-diabetes and fatty liver disease.

"Since muscle is very good at burning calories, the increased muscle in ursolic acid-treated mice may be sufficient to explain how ursolic acid reduces obesity. However, we were surprised to find that ursolic acid also increased brown fat, a fantastic calorie burner. This increase in brown fat may also help protect against obesity."

Until quite recently, researchers believed that only infants had brown fat, which then disappeared during childhood. However, improved imaging techniques have shown that adults do retain a very small amount of the substance mostly in the neck and between the shoulder blades. Some studies have linked increased levels of brown fat with lower levels of obesity and healthier levels of blood sugar and blood lipid, leading to the suggestion that brown fat may be helpful in preventing obesity and diabetes...

Take your exercise pill

Scientists may be able to come up with a pill that makes you want to exercise, thus solving -- sort of -- the nation's obesity epidemic. Swiss researchers have found that by elevating a hormone --erythropoietin (Epo) -- in mice, they were more motivated to exercise. To make this discovery, Gassmann and colleagues used three types of mice: those that received no treatment, those that were injected with human Epo, and those that were genetically modified to produce human Epo in the brain. Compared to the mice that did not have any increase in Epo, both mouse groups harboring human Epo in the brain showed significantly higher running performance without increases in red blood cells. "If you can't put exercise in a pill, then maybe you can put the motivation to exercise in a pill instead," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "As more and more people become overweight and obese, we must attack the problem from all angles. Maybe the day will come when gyms are as easily found as fast food restaurants."...

Tree oil may combat obesity, diabetes, S&T research suggests

A future weapon in the battle against obesity and diabetes could come in the form of an oil derived from the seeds of wild almond trees, according to researchers at Missouri University of Science and Technology. The key to the oil's potential lies in its ability to affect certain microorganisms living in our bellies. In a study presented today (Monday, June 18, 2012) at the American Society for Microbiology's general meeting in San Francisco, Missouri S&T researchers reported that adding sterculic oil to the diets of obese laboratory mice increased their sensitivity to insulin. This was due to the oil's effect on three types of microorganisms that live in the guts of the mice...

Higher dose of milk vitamin fights obesity

A novel form of vitamin B3 in milk given in a high dose to mice fed a fatty diet seemed to help prevent obesity, U.S. and Swiss researchers said. Dr. Anthony Sauve of Weill Cornell Medical College in New York and Dr. Johan Auwerx of Federal Polytechnic School in Lausanne, Switzerland, said high doses of the vitamin precursor, nicotinamide riboside -- a cousin of niacin -- prevented obesity in mice fed a fatty diet and also increased muscle performance, improved energy expenditure and prevented diabetes development, all without side effects. This form of vitamin B3 is found in milk in small quantities...

Fat-busting, super diet pill could help beat obesity by preventing those hunger pangs

A super diet pill aimed at curbing fat people's appetites could soon be a reality thanks to boffins who have found the secret to tackling obesity may lie in the brain. The pill would not only shrink waist lines but also the £4.2 billion NHS bill for treating obesity related illness such as cancer, diabetes and heart disease. Scientists in the US believe the hypothalmus area of the brain - a receptor controlling body temperature, hunger, thirst and fatigue - is particularly sensitive to drugs which could hold the key to fighting flab. Professor Domenico Accili, from Columbia University Medical Center, said: 'We've identified a receptor that is immediately involved in regulating food intake. 'What is especially encouraging is that it is a highly 'druggable' target. In fact, several existing medications already seem to interact with this receptor.' The researchers, whose findings are published in the Cell journal, studied insulin and leptin hormones, which inhabit the AgRP molecule and are vital to maintaining the body's energy balance. They did so by creating a strain of mice to explore the effects of appetite stimulation and discovered a gene called Gpr17. The scientists found that when the gene was injected into normal rodents, it resulted in an increase in appetite and a decrease when it was blocked - without negative side effects...

The miracle molecule: Hidden vitamin found in BEER and MILK can make you stronger, slimmer and healthier

If you were planning on having a quick pint tonight, then this will be welcome news. Beer may contain a vitamin which can fight obesity and improve muscle strength, scientists claim. The ‘miracle molecule’, which has been found in milk and may also be present in beer and some foods, has no side effects and could even lengthen lifespan, they say. The snag is that the molecule, called nicotinamide riboside (NR), is extremely small, difficult to find and expensive to synthesise. Johnan Auwerx, head of the Ecole Polytechnique Federale in Lausanne, Switzerland, said experiments using mice revealed the molecule’s potential. In an article in the specialist journal Cell Metabolism journal, Mr Auwerx called the results 'impressive' 'NR appears to play a role in preventing obesity,' said Mr Auwerx. Working with Weill Cornell Medical College in New York, his team found mice on a high-fat diet that were fed NR gained significantly less weight – 60 per cent – than mice eating the same diet without NR supplements. And none of the NR-treated mice had indications that they were developing diabetes, unlike the untreated mice. Mice which were fed NR supplements over a ten-week period had better endurance performance than those who were not...

Improving obesity-induced insulin sensitivity

In recent years, a growing body of evidence has linked inflammation to the development of insulin resistance. In insulin resistance, the hormone insulin is less effective in promoting glucose uptake from the bloodstream into other tissues. Obesity is a major factor that contributes to insulin resistance, which can eventually lead to type 2 diabetes. Previous studies have shown that proinflammatory molecules found in fat tissue decreases sensitivity of tissues to insulin. To identify drug targets that will improve insulin sensitivity, Dr. Jerrold Olefsky and colleagues from the University of California in San Diego investigated the role of G protein-coupled receptor 21 (GPR21) in insulin resistance and energy homeostasis. The group compared mice without the gene encoding GPR21 to healthy control mice under normal and high-fat diet conditions. They discovered that mice lacking GPR21 had enhanced insulin sensitivity and increased energy expenditure independent of diet. This result was attributed to the reduced migration of inflammatory cells to the liver and fat tissue in the absence GPR21. Under normal diet, absence of GPR21 in the hypothalamus caused a modest decrease in body weight. This is the first study to demonstrate the negative impact of GPR21 on inflammation and insulin sensitivity. Their findings suggest that GPR21 inhibition may improve insulin resistance and enhance energy expenditure, making GPR21 inhibitors promising treatments for diabetes.

Is There a 'Healthy' Obesity Gene?

Why is it that some obese people are healthier than others? This was one of the main questions Dr. Chaodong Wu of the College of Agriculture and Life Sciences -- Texas A&M University System -- and a group of researchers tried to answer in a recent study. The study, which will appear in a July issue of the Journal of Biological Chemistry, used genetically modified mice to investigate the genetic aspects of why some obese people do not develop certain medical problems typically associated with obesity, especially Type 2 diabetes. Wu noted that Xin Guo, a Ph.D. candidate in the college's department of nutrition and food sciences, contributed significantly to the study. "Previous research had indicated that a regulatory enzyme which is encoded by the gene PFKFB3 protects against diet-induced fat tissue inflammation and systemic insulin resistance," said Wu, who also has a Texas AgriLife Research appointment. "Increasing evidence shows that fat deposition, or amount, is not directly associated with the inflammation or insulin resistance in the development of obesity-related metabolic diseases." Wu said the inducible 6-phosphorofructo-2-kinase (iPFK2) enzyme links metabolic and inflammatory responses and may underlie what he refers to as "healthy" obesity. "While many obese people develop Type 2 diabetes, heart conditions and other chronic health problems associated with being significantly overweight, other obese people do not," he said. "And while obesity in general is not healthy, some obese people do not develop the diseases more commonly associated with a less-than-healthy diet. Furthermore, a number of thinner people may have the sort of health problems more typically associated with obesity." Wu said he and the other researchers theorized that these diseases are associated with the cellular inflammatory response brought on by obesity. "We also thought this gene could conceivably be targeted for use in the treatment of diabetes, especially Type 2, commonly associated with obesity," he said. "We wanted to find out what might happen to a subject if that particular gene was activated." Wu and his fellow researchers used laboratory mice to explore the effect of a targeted adipocyte overexpression of the gene/enzyme combination on diet-induced inflammatory responses and insulin sensitivity...

Timing of meals is tied to obesity

Gaining weight is not just the result of the number of calories eaten but also may have to do with the time of day those calories are consumed, at least in mice. The researchers, from the Salk Institute in California and elsewhere, fed the mice a high-fat diet or a standard diet. Some of the mice were allowed to eat only within an eight-hour period each day and the others were given an unrestricted amount of time to eat. When mice on the high-fat diet were restricted to eating within eight hours, they consumed just as much as those on the same diet who were permitted to eat around the clock. However, the mice with unrestricted eating times were more likely to become obese or have other metabolic disorders.

Gut Organisms Could Be Clue in Controlling Obesity Risk

The international obesity epidemic is widespread, nondiscriminatory, and deadly. But do we really understand all of the factors underlying this alarming trend? The concept of energy balance (energy consumed = energy expended + energy stored) is undeniable, being driven by the first law of thermodynamics. Consequently, there is no contradiction that excessive calorie intake and plummeting levels of physical activity are largely to blame for our ever-expanding waistlines. However, scientists remain baffled as to why some individuals are particularly prone to becoming obese and if there is anything aside from lowering calorie consumption and increasing activity levels that can be done to prevent and/or reverse excessive weight gain in our most at-risk populations. Physiologists have long known that our intestines are brimming with live bacteria, some of which provide important substances (e.g., vitamin B-12) to their host. However, research conducted over the last decade suggests that these organisms, often referred to as intestinal microbiota, may play a far greater role in human health than previously imagined. One area of intense interest is the possibility that the mix of intestinal bacteria with which we are endowed might directly influence our risk for obesity. Obese individuals tend to have different microbial profiles in their intestines than lean individuals, and scientists have learned that the bacteria common to obesity may metabolize the food we eat in a way that allows us to harvest more calories from it and deposit those calories as fat. To determine whether altering one's bacterial profile can change obesity risk, researchers from the French Institute for Agricultural Research (INRA) transferred the intestinal bacteria of obesity-prone or obesity-resistant rats into the intestinal tracts of germ-free mice recipients, therefore having no innate gut microbiota. Some animals were fed a regular diet, whereas others were provided unlimited access to a high-fat diet. Food intake and weight gain were monitored for 8 weeks, and intestinal samples were analyzed for a variety of physiologic markers of metabolism and normal feedback mechanisms known to play a role in maintenance of energy balance. As hypothesized, mice that received intestinal bacteria from obesity-prone animals ate more food, gained more weight, and became more obese than those receiving microbiota from obesity-resistant animals. Animals with microbiota transferred from obesity-prone animals also exhibited changes in intestinal nutrient sensors and gut peptide levels, likely influencing how the animals responded to eating. The authors' conclusions are three-fold. First, they theorize that obese individuals, when given the opportunity to overeat, may harbor specific gut microbiota profiles that promote excess weight gain. Second, they propose that differences in gut microbes can be related to behavioral changes and increased food intake. Finally, they believe that the mix of microbiota you have may influence your ability to properly sense and respond to a meal. They hope to eventually find ways to manipulate the intestinal microbiota profiles of especially at-risk individuals so that they can more easily maintain a healthy body weight...more

Men with low testosterone face increased risk of obesity and diabetes

MEN with low levels of testosterone could be at greater risk of developing diabetes, a study has suggested. Researchers from Edinburgh University found low testosterone levels are linked to a resistance to insulin, the hormone that controls blood sugar levels. • Research shows low testosterone levels “instrumental” in onset of diabetes • Men with low levels of testosterone are more likely to become obese Testosterone is present throughout the body and low levels are associated with increased obesity, a known risk factor for developing type 2 diabetes. But scientists said the study provides evidence of increased risk “even when body mass is not affected”. Dr Kerry McInnes, from the university’s endocrinology unit, said: “We know that men with low testosterone levels are more likely to become obese and as a result, develop diabetes. “This study shows that low testosterone is a risk factor for diabetes no matter how much a person weighs. As men age, their testosterone levels lower. This, along with increasing obesity, will increase the incidence of diabetes.” The research team said the study is the first to directly show how low testosterone levels in fat tissue can be “instrumental” in the onset of the condition. They said the findings show that mice with impaired testosterone function in fat tissue were more likely to be insulin-resistant. However, they also reveal that insulin resistance occurs in mice when testosterone function was impaired regardless of body weight...more

Nighttime fasting may foster weight loss

In an age of long commutes, late sports practices, endless workdays and 24/7 television programming, the image of Mom hanging up her dish towel at 7 p.m. and declaring "the kitchen is closed" seems a quaint relic of an earlier era. It also harks back to a thinner America. And that may be no coincidence. A new study, conducted on mice, hints at an unexpected contributor to the nation's epidemic of obesity — and, if later human studies bear it out, a possible way to have our cake and eat it too, with less risk of weight gain and the diseases that come with it...more

Manipulating Molecules in Heart Protects Mice On High-Fat Diets from Obesity, Affects Metabolism

UT Southwestern Medical Center researchers have demonstrated for the first time that the heart can regulate energy balance throughout the body, a finding that may point to more effective treatments for obesity, diabetes, and heart disease. Obesity, cardiovascular disease, and diabetes affect tens of millions of people in the U.S., according to the Centers for Disease Control and Prevention. Using mice fed a high-fat diet, researchers found that manipulating a heart-specific genetic pathway prevents obesity and protects against harmful blood-sugar changes associated with type 2 diabetes...more

Fat gene may predict protection against diabetes, study suggests

While obesity is a huge risk factor for type 2 diabetes, many people with 50 or 60 extra pounds to lose never develop the condition, and a new study from Beth Israel Deaconess Medical Center provides a possible explanation. It may have something to do with how much they express a particular gene in their fat cells; the gene makes cells more sensitive to the hormone insulin which transports glucose into cells. Normally, type 2 diabetes occurs when cells become resistant to insulin, causing blood sugar levels to rise to dangerously high levels. In the study published Sunday in the journal Nature, the researchers manipulated the “glucose transporter” gene in obese mice to allow more sugar into fat cells and found that the mice didn’t develop diabetes. On the flip side, normal weight mice who lacked the glucose transporter gene had soaring blood sugar levels. “We all have this gene but how much it’s turned on and expressed in our fat cells seems to be predictive of how metabolically healthy we are,” explained study co-author Dr. Barbara Kahn, an endocrinologist at Beth Israel Deaconess Medical Center. Those with high levels of expression get more protection from diabetes, while those with low levels have less protection...

New lab mice cut search for genetic links to disease by more than a decade

With a 95 percent genomic similarity to humans, mice have long been used to learn about the genetic causes of human disease. Once researchers can shine a light on the genetic factors that cause disease in mice, they can start to develop prevention and treatment options to protect the human population. But this process, called genetic mapping, is a long and difficult road, made more challenging by the 5% difference between the humans and lab mice. Now Prof. Fuad Iraqi of Tel Aviv University's Sackler Faculty of Medicine is closing the gap with an international project called Collaborative Cross. The project is developing lab mice with increased genetic diversity, making them more advantageous for genetic research related to human health. The new population will offer 1,000 genetic strains within a fixed genotype — the composite of the entire genetic makeup of an organism. This is a marked improvement on the previously existing 450 genetic strains of lab mice with varying genotypes, making Prof. Iraqi's new strain ideal for genetic mapping. And with these mice, researchers will be able to identify a gene associated with a particular disease within two to three years instead of the 10 to 15 years it takes now, says Prof. Iraqi...

Biologist claims certain chemicals increase chance of obesity

Obesity is at epidemic proportions in this country. But what if some people are overweight, not only because of the brownies they eat, but because of the plastic containers they store them in? The conventional theory goes that people become obese because they take in more calories than they burn off. But molecular biologist Bruce Blumberg says it’s more complicated than that. "If it were a simple problem, a matter of balancing our caloric checkbook, no one would be fat," says Blumberg. "We are not a country full of lazy people who just eat everything in sight." In his lab at UC Irvine, some of his mice are obese. Blumberg made them that way, but not by overfeeding them. "My mice become fatter on a normal diet," Blumberg explains. "That’s only because they were exposed to this chemical in the womb." The chemical he’s talking about is called Tributyltin. It’s used to preserve wood and is found in some vinyl products. There are more than a dozen kinds of drugs and chemicals that make lab animals — or people — fat. Blumberg calls them obesogens...

Fat mice provide genetic clues to obesity puzzle

A new study published in Nature Medicine provides clues as to how a gene mutation may lead to obesity. Mutations in the brain-derived neurotrophic factor gene (BDNF) have previously been shown to cause obesity in mice and have been identified in severely obese children. Genome-wide association studies have also confirmed BDNF as a susceptibility gene for common obesity in humans. The study investigated the mechanism by which BDNF mutations lead to obesity. Obesity is caused by an excess of energy, which can result from high energy intake, low energy expenditure, or both. Obesity was caused solely by overeating in mice with BDNF mutations, which consumed up to 80% more food than those without the mutation (‘wild type’ mice). When the mice with the mutation were restricted to the amount of food that that the wild type mice chose to eat, they did not become obese...

Study has shown to reverse obesity, body fat and improve insulin sensitivity in mice

Scientists used the ACE inhibitor captopril (CAP)—commonly used for the treatment of hypertension and cardiac conditions—and found that it can reduce the body weight of mice maintained on a high-fat diet. Initially, mice were put on a high fat diet for 12 weeks to produce mice with diet-induced obesity. During the subsequent 12 weeks treatment period, the mice were allowed access to the high-fat diet and either water containing CAP or plain tap water (the control). "From the first week of treatment, food intake and body weight decreased in the mice treated with CAP compared with the control mice. "Both peripheral insulin sensitivity and hepatic insulin sensitivity were improved in CAP treated mice compared with the control, which means there was an improvement in the handling of blood sugar," says Dr. Shirmila Premaratna, lead researcher from the La Trobe’s Faculty of Science, Technology and Engineering...

Skinny genes – how GM food may help you stave off obesity

Fond of a full English breakfast? Perhaps you should have a glass of blood orange juice on the side – it might help to reduce the harm from all the fat you are ingesting, and make you less likely to become obese.

But as blood oranges are among the least favoured fruits for consumers, scientists in the UK are hoping to find ways to genetically modify standard oranges to incorporate the beneficial effects of their less popular cousins.

The project is one of several aimed at improving health through the genetic modification of plants – a process that scientists say could be a low-cost answer to harmful nutritional deficiencies.

Another project involves incorporating algae genes into oilseed rape, in order to produce nutritionally vital fish oils without having to kill fish; and grains modified to take up more zinc from the environment, to alleviate the zinc deficiency that blights millions.

The scientists involved believe that the public will be more accepting of GM plants that plug common nutritional gaps, than those crops that benefit big companies. "This isn't about increasing the profits from multinationals – there are big gains to be had," said Prof Dale Sanders, director of the John Innes Centre, an independent centre for plant science and microbiology research.

Although only a handful of GM experiments are licensed in the UK at present, some lab research continues, although scientists are concerned that the science is moving elsewhere. Cathie Martin, also of the John Innes Centre, who is leading the research on blood oranges, said: "There are enormous problems in creating something that can be grown in Europe, and big problems in public funding, because of the regulation."

Unpublished research has suggested that compounds found within blood oranges could help to cut obesity by reducing the accumulation of fats, and so avoid some of the harm from fatty foods. In one human study, people fed a full English breakfast along with the juice of three blood oranges experienced less accumulation of fat, possibly because of substances known as anthocyanins, found in abundance in blood oranges.

The results should be taken with caution – they are unpublished and have not yet been peer-reviewed. Studies on mice have shown a similar effect, preventing obesity in mice fed a high-fat diet, compared to mice given ordinary orange juice, or water, but the human effects are still uncertain...

'Gluttony gene' stops mice feeling full

A mutation in a gene linked to obesity causes mice to eat up to 80 percent more than normal, a study suggests.

After eating, hormones send signals to the brain to let it know it's full. However, scientists found that in mice with a faulty version of the BDNF gene, these messages were 'blocked'.

'If there is a problem with the BDNF gene, neurons can't talk to each other, and the leptin and insulin [hormone] signals are ineffective, and appetite is not modified', said researcher Professor Baoji Xu from the Georgetown Medical Centre in the USA.

When the team monitored the eating habits of mice with and without the mutation, they found males were twice as heavy as their normal counterparts, and females were 2.7 times heavier. This was to do with them over-eating, rather than a reduction in their activity levels...