Gene links fertility and appetite

Researchers at the Salk Institute in La Jolla, California, US have found that the TORC1 gene in the brain controls both appetite and fertility. TORC1 acts as a 'master switch' that, when turned on, reduces food intake and allows pregnancy to occur, they report in the journal Nature Medicine. It is known that women who are underweight or obese can be infertile; the researchers believe that they have now found a gene involved in this process. 'It likely plays a pivotal role in how much we, as humans, eat, and whether we have offspring,' said Professor Marc Montminy, who lead the study.

TORC1 is a gene involved in the communication pathway between body fat and the brain and controls appetite.  When the body is well fed, the hormone leptin is produced by fat cells. Leptin is released into the bloodstream and travels to the hypothalamus in the brain, a region involved in appetite control. The TORC1 gene is switched on by leptin, which causes a decrease in appetite and allows reproduction to occur. When energy intake is low, for example during a food shortage, the body does not produce leptin. TORC1 remains switched off, appetite is not diminished, and fertility is reduced. Professor Montminy believes linking reproduction and food intake confers an evolutionary advantage by preventing pregnancy, which puts high energy demands on the body, when food is scarce. 'If there is no food, the brain believes that 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', he explained.

To investigate the link between fertility and food intake, the research group studied mice that lacked one or both copies of the TORC1 gene. Mice without the gene ate more than normal mice and had two to three times more fat, and were insulin resistant. 'Their hormones and blood sugar resembled that seen in humans with these disorders,' said Professor Montminy. In the mice lacking the TORC1 gene, the leptin from body fat cannot communicate with the brain, and the signal to reduce appetite and stop eating fails. Both male and female mice were also infertile. The research group found that KISS1, a gene required for normal reproduction, was regulated by TORC1. In the absence of TORC1, levels of KISS1 were low, leading to infertility.

Commenting on the study, Professor Bloom of Imperial College London said that 'it's an extremely interesting observation. We've known for a long time that if you haven't got any fat as a girl your periods stop, and if you give leptin, the periods start again', adding 'however, I don't think they have yet established whether this is just a stepping stone, or the key link in the chain'.