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Yo-yo mouse. Researchers may have found the key to failed diets, at least in rodents.

Why Diets Fail

Chilling out might be the key to losing the weight you gained over Thanksgiving. New research shows that dieting makes the brain more sensitive to stress and the rewards of high-fat, high-calorie treats. These brain changes last long after the diet is over and prod otherwise healthy individuals to binge eat under pressure.

Most research on weight loss has focused on tweaking appetite regulation—helping people eat less, get full faster, and have fewer cravings. But once we lose weight, we have trouble keeping it off. Even weight-loss surgery doesn't always help people maintain their more svelte physiques.

Maybe, thought Tracy Bale, a neuroscientist at the University of Pennsylvania, the problem is stress. Stress causes the body to release the hormone cortisol, which fuels the blood with energy in the form of sugar, enabling us to flee from potential dangers. Over time, high stress levels lead to chronically elevated cortisol levels that can cause increased appetite and weight gain.

Bale and her co-authors hypothesized that dieting leaves people more susceptible to the chronic stresses of everyday life, making even the strongest dieter yearn for a pint of ice cream or a hot, cheesy pizza. Although one hot fudge sundae won't cause significant weight gain, persistent stress could lead to a pattern of binge or comfort eating that undoes previous weight loss.

To test their hypothesis, the researchers cut daily food intake in mice by 25% for 3 weeks, until the rodents had lost about 10% to 15% of their original body weight. This regimen simulates a moderate diet and modest weight loss in humans. After exposure to mild forms of stress, such as loud noises, the hungry mice had higher levels of cortisol in their blood. And their cortisol levels stayed higher longer than in control mice. This indicates that the dieting mice were more stressed and took more time to calm down.

The mice were then allowed to return to their starting body weights to mimic yo-yo dieting, when people repeatedly lose and regain weight. After they had been eating standard lab chow for 1 week, the mice again underwent a series of mild stress tests to mimic the ups and downs of everyday life. The study, published today in The Journal of Neuroscience, reveals that ex-dieters remained more sensitive to stress than nondieters and were more likely to eat large amounts of high-fat mouse chow when under pressure.

Even this short, relatively mild food reduction resulted in long-term changes in gene expression, the researchers found. The mice that dieted had significantly higher levels of the protein that stimulates cortisol release, indicating higher sensitivity to stress. These mice also had higher levels of appetite-stimulating hormones after exposure to the high-fat binge food.

"This shows that environmental factors like dieting and exposure to high-fat foods can lead to long-term changes in gene expression that themselves may influence eating habits and stress response," says Cynthia Bulik, a psychologist and director of the Eating Disorders Program at the University of North Carolina, Chapel Hill, who was not involved in the study.

Changes in gene expression may help explain why so many diets fail. Dieting increases stress sensitivity, and stress makes us seek out rewarding things like high-fat, high-calorie "comfort" foods.

"Dieting is tough because your brain is working against you," Bale says. Learning better ways to cope with stress may be the key to successful weight loss because "you aren't prone to have stress drive you to want to consume." Bale thinks that designing medications to target these stress pathways may help dieters keep off the weight that they worked so hard to lose.