From Our 2008 Archives

Overeating Can Throw Off Metabolism

By Amanda Gardner
HealthDay Reporter

THURSDAY, Oct. 2 (HealthDay News) -- New research shows that overeating triggers a metabolic response normally dormant in the hypothalamus region of the brain, even when a person hasn't gained weight.

"We discovered a very general disease pathway in the hypothalamus, a structure in the middle part of the brain which functions to regulate appetite, feeding behavior, energy and therefore body-weight balance and metabolic processes," said Dr. Dongsheng Cai, senior author of a paper published in the Oct. 3 issue of Cell that details the findings.

"Persistent stimuli from excessive amount of calories can trigger this response before the overt onset of obesity, and this response when induced can promote overeating, contributing to increased levels of caloric overconsumption," Cai added. "So, this process can be like a vicious cycle."

Although the study was conducted in mice, the authors believe the findings will also apply to humans.

Suppressing the pathway might be a potent weapon in the war to fight the burgeoning epidemic of overweight and obesity and its attendant problems, including heart disease and even cancer.

Two-thirds of U.S. adults are overweight or obese; one-third are obese.

Current efforts to combat obesity -- namely dieting and exercise -- are rarely effective and certainly are not long-lasting.

"Exercise and diet may correct abnormal brain regulation [but] long-term food control is very difficult," said Cai, an assistant professor of physiology at the University of Wisconsin-Madison. "We don't understand why. . . The first important thing to understand is how the dysregulation of the brain is processed. The study we just did provides a new pathway. It's the opening of a new direction."

Until recently, researchers didn't know that the hypothalamus was important for how energy processing is conducted in the body.

"The brain is receiving more and more attention from the field . . . but nobody knows whether and how the hypothalamus could be responsible for the increasing occurrence of energy imbalance and obesity under today's environment typical of overnutrition," Cai explained.

Prior research had shown that eating too much triggered inflammatory responses in muscles, liver and other metabolic tissues, changes that underlie the development of type 2 diabetes. So the IKKb/NF-kB pathway had already been identified as a crucial player in these processes.

But it wasn't known if the same pathway was at work in the central nervous system.

In studying the brains of mice, Cai and his colleagues found that a high-fat or high-sugar diet did indeed increase the activity of this pathway in the brain as well. Similarly, the pathway is active in the brains of mice predisposed to obesity.

Once awakened, the pathway induces insulin resistance and dysfunctions of other hormones engaged with weight control and appetite.

While chronic inflammation was once thought to be a result of obesity, it now appears to promote it as well.

SOURCES: Dongsheng Cai, M.D., Ph.D., assistant professor, physiology, University of Wisconsin-Madison; Oct. 3, 2008, Cell

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