Controlling key enzyme in brain offers clue for future obesity treatment

December 15, 2009, Brown University
Controlling key enzyme in brain offers clue for future obesity treatment
Eduardo Nillni is a professor of medicine at Brown University. Credit: Photo Provided

The Sirt1 enzyme in the body has generated enormous attention as a possible secret to living longer. Some scientists believe that fasting and drinking wine appear to aid in this quest because both likely activate Sirt1, unleashing its power.

But researchers from Brown University, Rhode Island Hospital and the University of Texas Southwestern Medical Center have discovered that Sirt1 in the brain has its own potential health benefit: It may keep people thinner. They determined that inhibiting the activity of Sirt1 in the brain's hypothalamic region appears to help control food intake — a finding that potentially lays the groundwork for new treatments for obesity. Details will be published online Dec. 15, 2009, at .

The discovery is the culmination of the first in-depth study of the metabolic role of Sirt1 in the brain. It suggests that Sirt1 behaves differently in the brain than in organs such as the liver and pancreas, where the enzyme has been more commonly studied.

Sirt1 research so far has posited that fasting activates Sirt1 and thereby helps extend life. Drug companies and scientists have also thrown their support behind resveratrol, a compound found in , thought to be beneficial to the body because it may activate Sirt1. The new Brown research challenges at least some of the preexisting findings, because scientists found that inhibiting the activity of Sirt1 in the brains of rats, rather than stimulating it, appeared to reduce appetite, leading to a smaller weight gain compared to untreated animals. They believe a similar mechanism exists in human brains.

"It's still controversial whether calorie restriction or resveratrol are Sirt1 stimulators," said Eduardo Nillni, the study's lead author. Nillni is professor of medicine (research) at the Warren Alpert Medical School of Brown University and a member of the Department of Molecular Biology, Cell Biology and Biochemistry. At Rhode Island Hospital, Nillni is senior investigator in the Division of Endocrinology. Other authors include researchers from Brown and the University of Texas Southwestern Medical Center.

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 they generated clear data showing that pharmacologically or genetically inhibiting Sirt1 activity in the brain led to the animals eating less food and gaining fewer pounds compared to their untreated counterparts.

The study also indentified specific brain receptors or sites where Sirt1 induced food intake — the melanocortin receptors.

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

Related Stories

Recommended for you

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

mysticshakra
not rated yet Dec 15, 2009
I just love how people spend so much effort coming up with every way possible to avoid having to do any work. Controlling obesity isn't rocket science nor is it a secret. Control your calories and get plenty of exercise. Simple.

We don't need special drugs or secret formulas. We don't need special ab machines and it will definitely take for than minutes a day.

Stop being lazy and irresponsible. Stop enabling people by looking for a gutless solution for those unwilling to take responsibility for the condition of their own body.

Exercising daily is just as mandatory for health as consistent, proper eating and showering.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.