July 9, 2004 CORVALLIS, Ore. – A new study has found that a gene called SIRT1 can reduce the development of new fat cells and increase the metabolism or use of fat within existing fat cells.
SIRT1 is the topic of considerable recent research, and other studies have also shown that its activity level can be significantly increased by the presence of a compound found in red wine.
The new research, done by scientists from Oregon State University, the Massachusetts Institute of Technology and the University of Ottawa, was recently published in the journal Nature.
It may help explain, researchers say, why moderate consumption of red wine appears to reduce deaths from heart disease, as has been suggested by some demographic studies.
The study was done with mice as a research model, and a remaining challenge will be to see if the same results are observed in a higher vertebrate model, including humans.
The research outlined the processes of fat formation and usage at a cellular and genetic level. It also analyzed the metabolic function of resveratrol, a polyphenol and antioxidant found at high levels in grape skins.
"When cells were exposed to resveratrol, our studies showed a pretty dramatic reduction in the conversion to fat cells and a lesser but still significant increase in the mobilization of existing fat, or the rate at which the cells metabolized stored fat," said Mark Leid, a professor of pharmacology in the OSU College of Pharmacy. "This clearly could be one of the explanations for the health benefits that some researchers believe can be linked to moderate red wine consumption."
A range of studies, the OSU and MIT researchers said, have demonstrated that caloric restriction is one of the few proven methods to retard aging, improve cardiovascular health and extend mammalian lifespan.
Research done with yeast has shown that a gene called SIR2 tends to promote longevity, and that yeast cells die prematurely if this gene is deleted, Leid said. Previous studies have shown that resveratrol can increase the activity of SIR2 and increase the lifespan of yeast cells up to 70 percent. And it has also been found that SIRT1, a gene found in both mice and humans, has essentially the same function as SIR2 and the same reaction to stimulus by resveratrol.
In trying to determine the molecular basis for this genetic link to longevity, the new study found that SIRT1 increases the use of fat and reduces the formation of new fat cells – apparently it represses one or more fat-regulating proteins and other genes that drive fat storage following calorie restriction. This may have been an evolutionary adaptation for the body to sense short term famine and counter it by increasing the burning of stored body fat, researchers say.
The increased activity of SIRT1 in the presence of resveratrol is clearly of interest, the researchers said, but it's too early to be certain of its effects in humans.
"It would be very premature to suggest that supplements of resveratrol would have any benefits, because this compound oxidizes very quickly and easily loses its metabolic effectiveness," Leid said. "Because of that we have a hard time even studying it in a laboratory setting. But we do know that red wine has fairly high levels of the compound, and this study would suggest at least one mechanism for possible health benefits of red wine. It may help prevent fat development and storage."
Resveratrol is found in the skins of grapes, and its concentration in wine is a reflection of the time the skins are present during the fermentation process – because of that, the levels are much higher in red wine than in white wine or other products. Other sources of the compound include mulberries, peanuts, and some other plants.
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