Dieting May Plant Seeds of Weight Regain

Cutting calories encourages binge eating under stressful conditions years later.

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By Tina Hesman Saey, Sience News

Dieters may need to cut stress as well calories to keep weight off, a new study of dieting mice suggests.

Shaving calories triggers molecular changes in the brain that make mice more susceptible to stress and binge eating long after the diet ends, researchers report in the Dec. 1 Journal of Neuroscience. The finding could explain part of the yo-yo dieting phenomenon, in which people repeatedly diet and lose weight but then subsequently regain even more than they lost.

Researchers have well established that a low-calorie diet providing all an animal’s nutritional requirements can lengthen life. But Tracy Bale, a neuroscientist at the University of Pennsylvania in Philadelphia, wanted to know how cutting calories would, in the long term, affect the quality of that longer life.

To find out, Bale and her colleagues put some male mice on a diet. First the researchers fattened up mice by switching the rodents’ regular chow for a high-fat diet. Some of the mice were then put on a diet by switching them back to a regular diet, which amounted to a 25 percent calorie cut. After three weeks, the dieting mice had lost about 10 percent of their body weight. Human dieters also commonly lose about 10 percent of their body weight and then plateau, Bale says. Mice still on the high-fat diet kept gaining weight.

Dieting mice were more stressed than their high-fat-consuming counterparts, the researchers found. Levels of a hormone called corticotropin-releasing factor, or CRF, were lower in a part of the brain known as the bed nucleus of the stria terminalis. That part of the brain can dampen physical responses to stress generated in other parts of the brain. So turning down the activity of CRF there essentially releases a brake on the brain’s stress response, Bale says.

The team traced lower activity of the gene that makes CRF to a chemical modification called DNA methylation. DNA methylation and other modifications to genes help to regulate gene activity. Dieting mice had lower levels of methylated DNA near the gene for CRF than did animals that continued on the high-fat diet or ones that ate as much regular chow as they wanted. This change was essentially locked in for the dieting mice. It did not increase even two months after the diet ended—a long time in the life of a mouse, and equivalent to years, maybe even decades, for a person.

Those molecular changes corresponded to a heightened sensitivity to stress in the ex-dieter mice. After the dieting mice returned to a regular mouse-chow diet, all of the animals were given access to high-fat food for one hour each day. Both the mice that had never been on a diet and the dieters binged on the high-fat pellets when given a chance.

Researchers mildly stressed the mice for a week with things like damp bedding, cage swaps or putting a marble in the cage—mice are not big fans of change—so that the animals didn’t know what was coming next. Under this mild, but chronic, stress the former dieters snarfed down far more of the high-fat food than the nondieters. And the ex-dieters also had higher levels of hormones that prompt eating.

But if the dieter mice were more sensitive to stress, they were also more responsive to drugs that block the appetite-stimulating hormones, Bale’s team found. Given an appetite-suppressing drug, the ex-dieter mice ate less than never-dieter mice.

The new study “gives us an inkling about what may be going on in humans, but people shouldn’t jump to conclusions and think weight loss is impossible,” says Jeffrey Zigman, an endocrinologist and neuroscientist at the University of Texas Southwestern Medical Center at Dallas.

Dieters need to aware that stress could derail their progress and take steps to manage stress, says Bale.

Other researchers agree. “I don’t think it’s depressing; it just explains more about behavior,” says Uri Shalev, a behavioral neuroscientist at Concordia University in Montreal. On a diet, he says, “your mind becomes more sensitive to stress, and you should be aware of that.”