Too fat? Blame the thrifty gene

Looking beyond obvious causes of obesity like overeating, scientists said they may have found a gene that also plays a role, one that helped our ancestors survive famines.

Targeting this thrifty gene and others with diagnostic tests and drugs offers another way to fight the global epidemic of obesity, the researchers said.

Mice bred to lack this gene, known as CRTC3, can eat a high-fat diet without gaining weight, while normal mice on the same diet grow plump, the researchers found.

Mexican Americans who have an especially potent version of this gene are more likely to be obese than others, Dr Marc Montminy of the Salk Institute for Biological Studies in California and colleagues reported online in Nature.

The gene did not appear to have the same effect in Caucasians, which supports what scientists know - that obesity is very complex.

CRTC3 very important

"It slows down the rate at which the fat cells burn fat," Dr Montminy said of the gene in a telephone interview.

The findings lend more evidence to the theory of obesity made popular in the 1960s, which held that certain people have genes that slow metabolism, making it harder to lose weight.

These "thrifty genes would slow the rate of fat burning and increase your chances of surviving famine," Dr Montminy said.

Researchers are looking for ways to prevent and treat obesity - and countering the effects of a thrifty gene would be an obvious target.

Dr Montminy's team studied CRTC3 because it is very active in fat cells and is known to respond to signals that regulate fat burning.

"When we make animals that don't have the CRTC3 gene, these animals become lean," he said.

"If you feed them a diet that has up to 60% of calories from fat, their normal brothers and sisters that have the CRTC3 gene gain weight and become obese, insulin resistant and some go on to develop diabetes, but those who don't have the CRTC3 gene remain lean and insulin sensitive."

Effects on humans

The researchers looked for evidence of this same effect in people, and found it in a group of Mexican Americans who had a genetic mutation of the CRTC3 gene that makes it more potent than the wild form.

"Individuals with this variant had higher rates of obesity by several different measures," Dr Montminy said.

Interestingly, non-Hispanic whites who have this same genetic variant do not have higher rates of obesity.

"It means the therapies we come up with for diabetes or obesity will need to be a little bit more tailor-made, depending on the individual's genetic makeup," Dr Montminy said.

He said it may be possible to test people for the gene to predict who is likely to become obese, and it may even help predict who is at risk for obesity-related diseases like high blood pressure and type 2 diabetes.

(Reuters Health, Julie Steenhuysen, December 2010)

Read more:

Gene tests solve diet riddles

Obsesity and genetics

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