Brain 'Master Switch' May Control Appetite, Fertility

SUNDAY Aug. 31, 2008 -- A new study has found a "master switch" in the brain of mice that helps control both body weight and fertility.

It is well known that body weight and fertility are related to each other: Women who are too thin, for example, often have trouble getting pregnant. Now, researchers at the Salk Institute for Biological Studies may have found one reason why.

For a study published ahead of print in the Aug. 31 online edition of Nature Medicine, researchers studied a gene known as TORC1 in mice.

By creating mice that lacked one or both copies of TORC1, the researchers found that the gene affected both body weight and fertility. Specifically, the mice without the gene looked fine at birth, but at about eight weeks, they began to gain weight and became persistently obese in adulthood. And, to the researchers surprise, both sexes of these mice were infertile.

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

Montminy says that the TORC1 gene is just as important as the appetite-regulating hormone leptin, which turns on TORC1.

"Leptin tells the brain that times are good, your body is full, and that it is not necessary to eat more at the moment," said Montminy.

When leptin binds with its receptor in brain cells, it turns on TORC1, telling the body that it is well-fed and activating genes that suppress appetite and allow reproduction. When leptin is not activating the brain receptors, on the other hand, TORC1 is turned off, and the genes that suppress appetite and allow reproduction are inactive.

"Controlling appetite and reproduction together provides a big evolutionary advantage," Montminy said. "If there is no food, the brain believes the body should not reproduce, because without body fat, a baby's growth in the womb could be stunted, and without food to replenish the body's energy reserves, there will be nothing to feed the offspring."

The researchers also found that the mice that inherited only one TORC1 gene were able to reproduce but gained more weight than the normal mice.

"This suggests that half of the dose of TORC switch is enough to cause problems in leptin signaling in the brain, and it may be that subtle mutations in the TORC1 in humans could be responsible for an inheritable risk factor for gaining weight," said Montminy.

Montminy thinks that this research could lead to new therapies that tweak mutated and inefficient TORC genes.

"TORC1 is regulated by phosphate handling enzymes called kinases, and kinases often make for very good drug targets," he said.

More information

The American Society for Reproductive Medicine has more about weight and fertility.

Posted: August 2008


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