Minnesota researchers have identified a novel obesity-associated gene, according to a report by ScienceDaily. The gene, called CD38, caused laboratory mice to gain excessive weight when fed a high-fat, high-calorie diet, compared to mice that did not have the gene. The results of the study have been released in the online issue of The FASEB Journal, and will appear in the journal’s print form in November.
CD38 (cluster of differentiation 38) is a glycoprotein typically found on the surface of white blood cells, appearing as a result of cell activation. The glycoprotein has been found to be associated with many conditions, such as leukemia, type II diabetes, and HIV infection. It is also used as part of leukemia diagnosis. CD38 had previously been shown to regulate cell signaling pathways, especially those involved in energy metabolism. The Minnesota researchers had also previously demonstrated CD38’s role in the development of metabolic syndrome, a disease found primarily in obese individuals, which is marked by elevated blood pressure, insulin, and cholesterol levels.
Eduardo Chini and his colleagues tested two groups of laboratory mice: one which carried the CD38 gene, and one which did not. Both groups were fed a high-fat diet consisting of 60% calories from fat. Although both groups of mice consumed the same type of diet, only the group carrying CD38 gene became obese and exhibited symptoms of glucose intolerance (an indicator of diabetes). The CD38 positive group also lived about half as long as the CD38 negative group.
Further research indicated why CD38 had such a protective effect against obesity: the gene suppresses molecular pathways related to longevity. Calorie restriction has long been known to lower cholesterol and blood pressure, two of the symptoms of obesity-related metabolic syndrome, and to extend maximal life span. Calorie restriction also activates SIRT1, a gene linked to longevity. One of the actions of SIRT1 is the activation of peroxisome proliferator-activated receptor coactivator (PGC1), a key player in obesity and metabolism. Until now, the SIRT1-PGC1 activation/suppression reaction mechanism was unknown.
By selectively using sirtinol and resveratrol, two drugs that either shut down or activate SIRT, respectively, Chini and his colleagues were able to show that CD38 influences obesity via the SIRT1-PC1 pathway. Mice carrying CD38 and fed a high-fat diet, plus resveratrol (a SIRT1 activator), were protected from diet-induced obesity, indicating that the CD38 inhibits SIRT1-mediated pathways. Conversely, mice that were CD38 negative and fed a high-fat diet, plus sirtinol (a SIRT1 inhibitor), gained excessive weight.
Resveratrol is found naturally in foods like grapes, red wine, peanuts, and certain berries. It can also be manufactured. Chini and his colleagues are hopeful that the results of their research will be applied to obesity treatment and control by resveratrol, as well as to a better understanding overall of CD38-mediated obesity.
Sources:
Gene Deficiency Is A Protective Barrier To Obesity http://www.sciencedaily.com/releases/2007/06/070626115338.htm
Gene Deficiency is a Protective Barrier to Obesity: CD38 plays a role in regulating body weight and obesity http://www.mayoclinic.org/news2007-rst/4114.html
