A new study conducted on mice by researchers at the University of Iowa, found that ursolic acid, a compound found in apple peels, may help build muscle and fight obesity, glucose intolerance (characteristic of diabetes), and fatty liver disease.
If these results can be replicated in humans, the researchers suggested that their study points to a possible role for ursolic acid in fighting obesity and obesity-related illnesses, such as diabetes.
“These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness,” the researchers concluded.
The new study was published online in the Journal PLoS ONE, on June 20, 2012.
“Ursolic acid is a … [compound] that contributes to the waxy coats on apples, other fruits, and many herbs, including some folkloric herbal medicines for diabetes,” the University of Iowa researchers explained in an introduction to their study.
These same researchers previously had conducted studies on humans, in which they identified ursolic acid as a compound likely to function as an inhibitor of muscle atrophy. They then tested this hypothesis in other studies on mice, and found that ursolic acid reduced muscle atrophy in mice who had undergone surgical muscle denervation, and in fact increased muscle mass, reduced body fat, and lowered blood sugar in normal mice.
As to how ursolic acid functions, the researchers found that it activates a protein known as “Akt” in muscle tissue, which activates muscle growth and also increases energy expenditure (reduces obesity) and lowers blood sugar. The researchers explained,
Based on these earlier findings in normal mice, the University of Iowa scientists “hypothesized that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity, leading to muscle hypertrophy, increased energy expenditure and thus, reduced obesity, glucose intolerance and fatty liver disease.”
“In the current [new] study, we tested this hypothesis, and found that ursolic acid increases not only skeletal muscle, but also another tissue that opposes diet-induced obesity, brown fat,” the authors said.
The New Study; Methodology & Findings
In the new study, over a period of six weeks, the researchers fed one group of mice a high-fat diet (55% calories from fat) known to cause obesity, as well as glucose intolerance and fatty liver disease. Over the same six-week period, they fed a second group of mice the same high-fat diet, supplemented with 0.14% ursolic acid.
The researchers found that the mice fed the diet that included ursolic acid gained less weight and were less likely to develop conditions similar to pre-diabetes and fatty liver disease, even though they ate more food than the mice that did not consume the ursolic acid compound. There was no difference in physical activity between the two groups of mice, the researchers said.
At the end of the six weeks, the researchers examined samples of the triceps muscle of both groups of mice, and measured the mice’s energy expenditures. They found that the mice fed ursolic acid burned more calories than those that did not consume the ursolic acid in their diet.
The researchers further found that the mice that consumed ursolic acid developed more muscle mass, and more calorie-burning brown fat, than mice eating the same diet without the ursolic acid.
“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,” lead researcher Dr. Christopher Adams, an associate professor of internal medicine at the University of Iowa, told MSNBC.
However, the increase in brown fat was an unexpected finding. Brown fat may also help protect against obesity, Dr. Adams said.
According to the researchers, other studies have found that increased levels of brown fat are associated with lower levels of obesity, and healthier levels of blood sugar and fats. Thus, previous evidence suggests that brown fat may be helpful in preventing obesity and diabetes.
“Brown fat is beneficial and people are trying to figure out ways to increase it,” Dr. Adams said.
The researchers have not similarly tested the effects of ursolic acid in people, and research in mice does not necessarily produce the same findings as in humans. “We don’t know if ursolic acid will benefit people,” Dr. Adams noted.
However, he said, it’s possible that the compound could someday be used as a treatment for muscle atrophy, a condition that occurs in all people with aging. In addition, the new study suggests possible uses for ursolic acid in treating conditions involving metabolic syndrome, like pre-diabetes and diabetes, as well as in fighting obesity.
People with metabolic syndrome have at least three major risk factors for heart disease — such as too much abdominal fat, high triglycerides and high blood pressure.
“Our next step is to determine if ursolic acid can help patients,” Dr. Adams said.
The new study was funded by grants from the National Institutes of Health, the Department of Veterans Affairs, the University of Iowa Research Foundation, as well as the Fraternal Order of Eagles Diabetes Research Center at the University of Iowa.
The authors do disclose, as potentially competing interests, that the University of Iowa Research Foundation has applied for patents related to this work (WO/2011/146768/A1, /PCT/US2011/037238, Methods for Inhibiting Muscle Atrophy), and that Dr. Christopher M. Adams is a co-founder and officer of Emmyon, Inc., a company apparently dedicated to commercializing inventions related to such patents. They however declare that “This does not alter the authors’ adherence to all the [Journal] PLoS ONE’s policies on sharing data and materials.”
The new study, Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease, published June 20, 2012, is available in its entirety online from the publisher, the Journal PLoS ONE.
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