Apple peel compound boosts brown fat, reduces obesity in mice

ScienceDaily (June 20, 2012) — 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.

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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.

The UI team, which also included Steven Kunkel, Christopher Elmore, Kale Bongers, Scott Ebert, Daniel Fox, Michael Dyle, and Steven Bullard, studied mice on a high-fat diet over a period of several weeks. Half of the animals also received ursolic acid in their high-fat food. Interestingly, mice whose diet included ursolic acid actually ate more food than mice not getting the supplement, and there was no difference in activity between the two groups. Despite this, the ursolic acid-treated mice gained less weight and their blood sugar level remained near normal. Ursolic acid-treated mice also failed to develop obesity-related fatty liver disease, a common and currently untreatable condition that affects about one in five American adults.

Further study showed that ursolic acid consumption increased skeletal muscle, increasing the animals' strength and endurance, and also boosted the amount of brown fat. Because both muscle and brown fat burn calories, the researchers investigated energy expenditure in the mice and showed that ursolic acid-fed mice burned more calories than mice that didn't get the supplement.

"Our study suggests that ursolic acid increases skeletal muscle and brown fat leading to increased calorie burning, which in turn protects against diet-induced obesity, pre-diabetes and fatty liver disease," Adams says. "Brown fat is beneficial and people are trying to figure out ways to increase it. At this point, we don't know how ursolic acid increases brown fat, or if it increases brown fat in healthy mice. And, most importantly, we don't know if ursolic acid will benefit people. Our next step is to determine if ursolic acid can help patients."

The research was supported by funding from the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa, the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (grant 5R01AR059115-03), the Department of Veterans Affairs, and the University of Iowa Research Foundation.

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Scientists identify protein that stimulates brown fat to burn calories

ScienceDaily (May 10, 2012) — Scientists have identified a protein which regulates the activation of brown fat in both the brain and the body's tissues. Their research, which was conducted in mice, was published May 11, in the journal Cell.

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Unlike white fat, which functions primarily to store up fat, brown fat (also known as brown adipose tissue) burns fats to generate heat in a process known as thermogenesis. The research, led by scientists at the University of Cambridge Metabolic Research Laboratories at the Institute of Metabolic Science, discovered that the protein BMP8B acts on a specific metabolic system (which operates in the brain and the tissues) to regulate brown fat, making it a potential therapeutic target.

The scientists believe that activating brown fat could help to support current weight loss programmes, which individuals often struggle to maintain.

Dr Andrew Whittle, one of the authors of the paper from the Institute of Metabolic Science, said: "Other proteins made by the body can enhance heat production in brown fat, such as thyroid hormone but often these proteins have important effects in other organs too. Therefore they are not good targets for developing new weight loss treatments. However, BMP8B seems to be very specific for regulating the heat producing activity of brown fat, making it a more ideal mechanism for new therapies."

The experiments showed that when mice lacked the protein BMP8B they found it more difficult to maintain their normal body temperature. They also became much more obese than normal mice, particularly when fed a high-fat diet. Additionally, when the researchers treated brown fat cells with BMP8B they responded more strongly to activation by the nervous system. Furthermore, when BMP8B was administered to specific parts of the brain it increased the amount of nervous activation of brown adipose tissue. The result was that these BMP8B-treated brown fat cells burned more fat and mice given BMP8B in the brain lost weight.

Professor Toni Vidal-Puig, lead author of the study from the Institute of Metabolic Science and a member of the MRC Centre for Obesity and Related Metabolic Diseases, said: "A major feature of current weight-loss strategies is that people lose a lot of weight early on, but then reach a plateau despite continuing to follow the same diet regime. This is because the human body is incredibly good at sensing a reduction in food consumption and slows the metabolic rate to compensate. A strategy to increase brown fat activity could potentially be used in conjunction with current weight loss strategies to help prevent the typical decrease in a person's metabolic rate.

"One could be sceptical that techniques to increase metabolic rate might just be compensated by the body trying to make you want to eat more, to fuel this increased metabolism. But our findings showed that treating mice with Bmp8b did not have this effect, it simply made them lose weight by burning more fat in their brown adipose tissue.

"There are obvious differences between mice and humans, and from a therapeutic perspective this work is preliminary. Validation will be necessary to see if manipulating BMP8B would be safe and effective in humans."

The research was funded by the Medical Research Council (MRC), the Wellcome Trust, and the Biotechnology and Biological Sciences Research Council (BBSRC).

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