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Spring 2014
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Live Longer and Thinner
An enzyme holds the key.
Weight loss and longevity are two well-known health benefits of Sirt1, an enzyme that may be naturally activated in the body by fasting and drinking red wine. But what does Sirt1 do in the brain? Brown researchers, led by Eduardo Nillni, professor of medicine (research), recently published the first in-depth study of the metabolic role of Sirt1 in the brain.

Until recently, research indicated that fasting activates Sirt1 and thereby helps extend life. Drug companies and scientists have also thrown their support behind resveratrol, a compound found in red wine, thought to be beneficial because it may also activate Sirt1. Nillni’s team found that inhibiting rather than stimulating Sirt1 in the brains of rats appeared to reduce appetite, leading to a smaller weight gain compared to untreated animals. They believe a similar mechanism exists in humans, potentially laying the groundwork for new treatments for obesity.

“It’s still controversial whether calorie restriction or resveratrol are Sirt1 stimulators,” says Nillni. His team did confirm that fasting helped increase Sirt1 production and activity in the brain. And they generated clear data showing that inhibiting Sirt1 activity in the brain led the animals to eat less and gain less compared to their untreated counterparts.

The study also identified specific brain receptors or sites where Sirt1 induced food intake—the melanocortin receptors. Nillni says that more work needs to be done to investigate whether or how the brain pathways involving Sirt1 and food intake are affected in obese animals.

The study first appeared online on December 15, 2009, in the journal PLoS ONE.

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