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It’s the million-dollar (possibly billion-dollar) weight loss question: How do you keep lost weight off? This question is receiving renewed attention after a recent study reported that most of the contestants on Season 8 of television’s “The Biggest Loser” regained the large amounts of weight they’d lost on the show. Studies in rodents and humans show that soon after dieting or exercising stops, fat rapidly comes back and insulin resistance and glucose tolerance deteriorate. A number of physiological factors contribute to this rebound, including increased appetite and slower metabolism, but new research reports that stress hormones called glucocorticoids may also have a role.

In the study, rats were fed less and ran everyday on a running wheel for three weeks. The rats were then allowed to be sedentary and eat as much food as they wanted. After one week of this relaxed lifestyle, the rats had more fat tissue and worse glucose tolerance and insulin sensitivity than when they were dieting and exercising. But, when given mifepristone—a drug that blocks glucocorticoid hormone activity—during the relaxed week, the rats gained back less weight and their metabolic health didn’t change.

Dieting and exercising is stressful on the body, the researchers wrote, and the stress may prime the body to get back the fat it lost when the dieting and exercising stops. The study finds that glucocorticoid hormones are involved in this process and that preventing their action can reduce weight regain and metabolic changes.

While a miracle pill to keep the weight off may sound like a great solution, the researchers noted that the exercising and dieting rats were still healthier than the rats taking mifepristone. It’s important to emphasize the health benefits of regular exercise and a proper diet, they wrote. While a lifestyle change is the key to keeping weight off, it’s much easier said than done, as the “The Biggest Loser” contestants demonstrate.

Maggie Kuo, PhD, is the former Communications and Social Media Coordinator for APS. Catch more of her writing in the Careers Section of Science Magazine.