Obesity prevented in rats fed high-fat diet

Researchers at Washington University School of Medicine in St. Louis, United States (U.S.), have identified a way to prevent fat cells from growing larger, a process that leads to weight gain and obesity. By activating a pathway in fat cells in mice, the researchers found they could feed the animals a high-fat diet without making them obese.

The study is published online December 5 in the journal eLife.

“This could lead us to a new therapeutic target for treating obesity,” said senior investigator Fanxin Long, PhD, a professor of orthopedic surgery. “What’s particularly important is that the animals in our study ate a high-fat diet but didn’t gain weight, and in people, too much fat in the diet is a common cause of obesity.”

Long’s research focused on the so-called Hedgehog protein pathway that is active in many tissues in the body. His team engineered mice with genes that activated the Hedgehog pathway in fat cells when those animals ate a high-fat diet.

After eight weeks of eating the high-fat diet, control animals whose Hedgehog pathways had not been activated became obese. But the mice that had been engineered with genes to activate the pathway didn’t gain any more weight than did control animals that consumed normal diets.

The Hedgehog pathway prevented obesity by inhibiting the size of the fat cells, Long said.

“Fat gain is due mainly to increased fat cell size,” he explained. “Each fat cell grows bigger so that it can hold larger fat droplets. We gain weight mainly because fat cells get bigger, as opposed to having more fat cells.”

By stimulating Hedgehog and related proteins in fat cells, Long’s team kept the animals’ fat cells from collecting and storing fat droplets.