Brain \'Master Switch\' May Control Appetite, Fertility

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It is well known that body weight and fertility are related to eachother: Women who are too thin, for example, often have troublegetting pregnant. Now, researchers at the Salk Institute forBiological Studies may have found one reason why.
For a study published ahead of print in the Aug. 31 online editionofNature Medicine, researchers studied a gene known as TORC1 inmice.
By creating mice that lacked one or both copies of TORC1, theresearchers found that the gene affected both body weight andfertility. Specifically, the mice without the gene looked fine atbirth, but at about eight weeks, they began to gain weight andbecame persistently obese in adulthood. And, to the researcherssurprise, both sexes of these mice were infertile.
"This gene is crucial to the daisy chain of signals that runbetween body fat and the brain," study author Marc Montminy, aprofessor in the Clayton Foundation Laboratories for PeptideBiology, said in a Salk Institute press release. "It likely plays apivotal role in how much we, as humans, eat and whether we haveoffspring."
Montminy says that the TORC1 gene is just as important as theappetite-regulating hormone leptin, which turns on TORC1.
"Leptin tells the brain that times are good, your body is full, andthat it is not necessary to eat more at the moment," said Montminy.
When leptin binds with its receptor in brain cells, it turns onTORC1, telling the body that it is well-fed and activating genesthat suppress appetite and allow reproduction. When leptin is notactivating the brain receptors, on the other hand, TORC1 is turnedoff, and the genes that suppress appetite and allow reproductionare inactive.
"Controlling appetite and reproduction together provides a bigevolutionary advantage," Montminy said. "If there is no food, thebrain believes the body should not reproduce, because without bodyfat, a baby's growth in the womb could be stunted, and without foodto replenish the body's energy reserves, there will be nothing tofeed the offspring."
The researchers also found that the mice that inherited only oneTORC1 gene were able to reproduce but gained more weight than thenormal mice.
"This suggests that half of the dose of TORC switch is enough tocause problems in leptin signaling in the brain, and it may be thatsubtle mutations in the TORC1 in humans could be responsible for aninheritable risk factor for gaining weight," said Montminy.
Montminy thinks that this research could lead to new therapies thattweak 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 .
SOURCE: Salk Institute, news release, Aug. 31, 2008