Whileyou may blame mom’s home cooking for widening your waistline this holiday season, the more likely culprit is a far more distant relative. New research reveals that overactivity of an energy-regulating gene important to our ancient ancestors could play a major role in obesity. For decades, scientists have speculated about the existence of “thrifty genes,” ones that cause the body to burn fat for energy slowly to make it last. That would have been beneficial in hunter-gatherer times when fatty meals were often few and far between, said the current study’s lead author, Marc Montminy, a biologist at the Salk Institute in La Jolla, Calif. Such a gene would be less useful in today’s world where fatty food is all-too-easy to come by, he said, and would cause the body to store unnecessary amounts of fat. Sixty percent of U.S. residents are overweight, Montminy said, and the incidence of type 2 diabetes is on the rise.
“A thrifty gene would have been advantageous to our ancestors who went a long time between meals,” he said. “It’s not advantageous for those of us who enjoy an occasional taco.”
But the thrifty genes themselves have proven elusive. Montminy and his team decided to look at the effects of a candidate, the gene CRTC3, about which scientists knew little except that it was involved in metabolism within fat cells.
The researchers fed high-fat diets to both normal mice and mice genetically engineered without a functioning CRTC3 gene. The normal mice plumped up as expected, but the modified mice remained relatively lithe by comparison.
Since the gene is present in humans as well as mice, Montminy next wanted to see if they could find similar effects in people. The researchers looked at genetic information on file from 779 patients at Cedars-Sinai Medical Center in Los Angeles and identified those with a common, yet especially potent, version of CRTC3.
If lack of the gene in mice resulted in skinny mice, the researchers predicted that an overactive version of the gene in humans might result in obese people. That’s exactly what they found, with those carrying the overactive gene significantly more likely to have higher weights, body mass indexes and hip circumferences. The researchers published their findings this week in the journal Nature.
Of course, not everyone with this gene variant will become obese and not every obese person will develop type 2 diabetes, Montminy said, but screening for it could help doctors assess who’s at risk and develop drugs and therapies to counter its effects.
Juergen Naggert, a geneticist who studies obesity and type 2 diabetes at the Jackson Laboratory in Bar Harbor, Maine, said the study is an important one, but that more work needs to be done to show that an overactive CRTC3 gene is causally responsible for obesity. As it stands, it’s likely only one piece in the obesity puzzle.
“In the big scheme, it’s probably one of the many things that have an effect on obesity,” he said.
