Study: Enzyme linked to weight loss

A new study of the Sirt1 enzyme, which has made headlines as a possible key to longevity, has found a potential benefit to inhibiting, rather than stimulating, the enzyme’s activity in the brain: It seems to reduce appetite and thus may help keep people thinner.

The study, conducted by researchers from Brown University, Rhode Island Hospital and the University of Texas Southwestern Medical Center in Dallas, is the first in-depth look at the metabolic role of Sirt1 in the brain. Previous studies had focused mostly on the liver and pancreas, where Sirt1 appears to behave differently.

The study’s findings were published Tuesday at PLoS One, a peer-reviewed online publication of the Public Library of Science (read it here).

Working with rats, the researchers found that inhibiting the activity of Sirt1 in the brain’s hypothalamic region appears to help control food intake. They believe the same would happen with humans, offering a possible new treatment for obesity.

Sirt1 research so far had found that fasting activates Sirt1 and had linked that to a longer life. Resveratrol, a compound found in red wine, is also believed to activate Sirt1, so drug companies and researchers have paid great attention to it.

However, the new study, funded by the National Institutes of Health, challenges at least some of the older findings, because scientists found benefits in inhibiting, rather than stimulating, the activity of Sirt1 in rats’ brains.

“It’s still controversial whether calorie restriction or resveratrol are Sirt1 stimulators,” said Eduardo Nillni, the study’s lead author, a professor of medicine at the Warren Alpert Medical School of Brown University, and senior investigator in endocrinology at Rhode Island Hospital.

Nillni’s team did find that fasting helped increase Sirt1 production and activity in the brain, consistent with the view that reducing food intake stimulates Sirt1 elsewhere in the body, but then they showed that pharmacologically or genetically inhibiting Sirt1 activity in the brain led to the rats eating less food and gaining less weight. They also identified specific brain receptors or sites where Sirt1 induced food intake – the melanocortin receptors.

Nillni said more work should be done to investigate whether or how the brain pathways involving Sirt1 and food intake are affected in obese animals.