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New master switch found in the brain that regulates appetite and reproduction

LA JOLLA, CA Body weight and fertility have long known to be related to each other women who are too thin, for example, can have trouble becoming pregnant. Now, a master switch has been found in the brain of mice that controls both, and researchers at the Salk Institute for Biological Studies say it may work the same way in humans.

Findings from the study, published ahead of print in the Aug. 31 online edition of Nature Medicine, suggest that variations in the gene that produces this master switch, known as TORC1, could contribute a genetic component to obesity and infertility, and might be regulated with a novel drug.

"This gene is crucial to the daisy chain of signals that run between body fat and the brain," says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. "It likely plays a pivotal role in how much we, as humans, eat and whether we have offspring."

It is just as important as leptin, the well-known star regulator of appetite, Montminy says, because leptin turns on TORC1, which in turn activates a number of genes known to help control feeding and fertility.

Judith Altarejos Ph.D., first author on this study, had been trying to understand human energy balance, and what can go awry to promote obesity, diabetes and other metabolic syndromes. In this study, she looked at the signals that travel from body fat to the brain, informing the brain of how well fed the body is. The primary hormone that performs that function is leptin, which travels through the bloodstream to the hypothalamus in the brain (the appetite center), keeping the brain aware of the body's nutritional status.

"Leptin tells the brain that times are good, your body is full, and that it is not necessary to eat more at the moment," Montminy says. The hormone also is known to play a role in reproduction - although, until this study, no one understood what is was. (Very thin women of

Contact: Gina Kirchweger
858-453-4100 x1340
Salk Institute

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