Obesity linked to altered appetite control center

NEW YORK (Reuters Health) - Studies in obese mice suggest that a sensor in the brain that normally detects the fat hormone leptin -- causing a series of events that keep energy balance in check -- goes awry in the setting of obesity.

"Obesity is not a failure of will power, it is a biological failure. The brain is not aware that the body is obese," Dr. Michael Cowley of Oregon Health and Science University in Beaverton commented in a statement from Cell Press, which published the research in the journal Cell Metabolism.

Leptin, which is secreted by fat cells, normally prevents overeating by affecting brain cells that control appetite. However, high levels of leptin, which often accumulate in obese people, can lead to leptin resistance, meaning the body no longer responds to the hormone's appetite-suppressing signal.

The current research shows how a portion of the brain called the arcuate nucleus, which is critically important for leptin sensing, is "negatively impacted by an overabundance of leptin," explained Cowley.

For 20 weeks, Cowley and colleagues fed mice a high-fat or low-fat diet. Most, but not all, of the animals in high-fat diet group became obese and developed symptoms of diabetes, as is often the case in people. The low-fat diet group did not develop these health problems.

Leptin levels in the obese mice, but not the lean mice, rose dramatically and the obese animals, for the most part, became resistant to the weight-controlling effects of leptin. Mice with diet-induced obesity failed to recognize "any element of the leptin signaling cascade" that controls appetite, the authors report.

Importantly, the obese, leptin-resistant mice lost weight and regained their sensitivity to leptin when the amount of fat in their diets was reduced. This was a "nice surprise," Cowley said. "We had thought it might be more irreversible than that."

These findings "strongly support" the case that reduced sensitivity to the fat hormone leptin in critical brain regions is a cause of diet-induced obesity.

The research also supports prior studies which have suggested that a protein called SOCS-3 may be responsible for the loss of sensitivity to leptin. Therefore, treatments designed to inhibit SOCS-3 may help thwart leptin resistance in cases of obesity, perhaps restoring energy balance leading to weight loss, the investigators offer.

SOURCE: Cell Metabolism, March 2007.