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Jun 27, 2007

Researchers Discover Role of Gene in Obesity Pathway

  • A Study by the Mayo Clinic done in laboratory mouse models points to the absence of a gene called CD38. When absent, the gene prevented mice on high-fat diets from gaining weight, but when present, the mice became obese.

    Previous research in animal models has shown that caloric restriction can turn on the SIRT1 gene. In addition, the SIRT genes activate PGC1 (peroxisome proliferator-activated receptor coactivator), which can offset the negative effects of obesity in mice. However, how the SIRT-PGC1 reaction works hasn’t been explained until now, reported the researchers.

    In previous laboratory studies by the Mayo Clinic research team, CD38 was shown to be involved in regulating a wide variety of signaling pathways such as those that regulate energy metabolism. In this study, researchers investigated and confirmed that CD38 inhibits SIRT and the expression of PGC1 in mouse models and, as a result, regulates body weight. In the absence of CD38, the SIRT-PGC1 pathway was activated and the mice models were protected from developing obesity.

    Researchers studied two groups of mice: one with the gene CD38 and the other without. Each group was fed a high-calorie diet with 60% of the calories coming from fat. A second group was fed a standard diet in which 4% of the calories came from fat.

    As a result, the body fat of mice that carried CD38 and were on a high-fat diet nearly quadrupled and their body weight almost doubled. After eight weeks on a high-fat diet, mice with CD38 began to show signs of glucose intolerance, one of the first indicators of diabetes onset. In addition, this group of mice lived only four to six months, compared to the second group of mice that lived for 12 months.

    For the group of mice that did not carry CD38, body fat and weight did not change even though they were on a high-fat diet. These mice burned more energy, were leaner, and otherwise healthy.

    The researchers also examined the effects of resveratrol in mice. Resveratrol is a naturally occurring substance found in some plants such as mulberries, peanuts, and red grapes.

    Mice with CD38 were treated with 30 mg of resveratrol per day. And, to determine the effects of the SIRT genes on obesity, mice without CD38 received the same dose of sirtinol, a drug that shuts down the SIRT genes.

    Researchers found that mice with CD38 that were treated with resveratrol for two weeks were protected from high-fat, diet-induced obesity. In contrast, mice without CD38, but treated with sirtinol gained a statistically significant amount of weight when compared with mice without the gene who were not treated with sirtinol.

    The findings were published in the June online issue of The FASEB Journal.



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