Master switch found to regulate appetite, reproductionSeptember 1st, 2008 - 3:53 pm ICT by IANS
Washington, Sep 1 (IANS) Body weight and fertility have long been 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 mice brain that controls both, and researchers at the Salk Institute for Biological Studies said it may work the same way in humans.
These findings 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,” said Marc Montminy, professor at 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 said, because leptin turns on TORC1, which in turn activates a number of genes known to help control feeding and fertility.
Judith Altarejos, co-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 centre), 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 said. The hormone also is known to play a role in reproduction - although, until this study, no one understood what is was. (Very thin women often do not have periods.)
“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.”
“Leptin works remarkably well to give the brain a good indication of how much food has been eaten; 99.9 percent of the time it balances food intake with energy use,” he said. “The problem is that no machine works 100 percent of the time, and that slight bit of inefficiency can lead to extra body weight.”
Obesity results when the brain becomes “deaf” to the leptin signal, so one goal of Montminy’s research is to “try to make a way to make sure the brain signals are being heard.” But to do that, he and his research team first have to understand all of the signals involved in the satiety pathway.
Through years of research, they have uncovered a family of genes that act as energy switches, turning other genes on or off. For instance, mice born without TORC1 looked fine at birth, but at about eight weeks, they began to gain weight and became persistently obese in adulthood, with two to three times as much adipose fat as normal mice, and they also became insulin resistant. “Their hormones and blood sugar resembled that seen in humans with these disorders,” Montminy said.
The results were published in the Sunday online edition of Nature Medicine.