Researchers have identified six genes that may play a role in our appetite and, as a result, in whether we're plump or thin. They report in Nature Genetics that the genes appear to affect brain activity that controls how much we eat, indicating that obesity, at least in part, may stem from behavior passed on from one generation to the next.

The GIANT Consortium, an international group of scientists from over 60 institutions worldwide, compared the body mass index (BMI), a standard measure of body fat, with the genetic makeup of 90,000 people of European ancestry. Their findings: that slimmer folks had different versions of the six genes than their flabbier compeers.

Study co-author Elizabeth Speliotes, an internist at Massachusetts General Hospital, says the genes control activity in the brain's cortex (involved in decision making) and hypothalamus (which regulates appetite), indicating that the brain is a key factor in weight. But she notes that it's unclear exactly how the genes may affect hunger.

Joel Hirschhorn, a human geneticist at Broad Institute of the Massachusetts Institute of Technology and Harvard University, says that the genes individually have very little effect on a person's Body Mass Index (BMI), which correlates with body fat. In other words, it's unlikely that a mutation in one of the six would predispose one to being overweight (BMI of 25 to 29.9) or obese (BMI of 30 or greater)—these numbers are obtained by dividing a person's weight in kilograms by the square of the person's height in meters. But it could make a difference if several or all of them are flawed. "The effects of these genes start to add up," Hirschhorn says.

People with the greatest number of mutations in these obesity genes carried an average of 10 pounds more of fat than did those with the fewest.

"I think that this work is fantastic," says Liangyou Rui, an assistant professor of molecular and integrative physiology at the University of Michigan Medical School who is an expert on the genetic links to obesity in mice. He says the research may pave the way for new treatments for preventing and reversing obesity and obesity-related diseases.
"Each of the genes identified becomes a potential drug target," says study coauthor Goncalo Abecasis, a statistical geneticist at the University of Michigan in Ann Arbor.

So far, scientists have identified at least 10 genes associated with BMI, according to Hirschhorn, who says there are probably "hundreds of genes and certainly many genetic variants to be found" that may affect whether we're hefty or trim.

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