Researchers at Washington University School of Medicine in St. Louis have found a way to stop fat cells from getting larger, even when the animals are fed a high-fat diet. The work was published yesterday in eLife.
"This could lead us to a new therapeutic target for treating obesity," said senior investigator Fanxin Long, Ph.D., 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 Hedgehog protein pathway. They 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, their control mice (animals without an activated Hedgehog pathway) became obese. However, their engineered mice did not gain any more weight than the control animals that consumed normal diets.
"The Hedgehog pathway prevented obesity by inhibiting the size of the fat cells," said Long.
"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."
The stimulation Hedgehog and related proteins kept the animals' fat cells from collecting and storing fat droplets.
"More importantly, when we did metabolic studies, we found that the animals with the active Hedgehog pathway not only were leaner, they also had lower blood-glucose levels and were more sensitive to insulin," he said.
Long believes that there could be potential to fighting obesity in humans with a treatment that targets the Hedgehog pathway. However, much caution would need to be taken as there could be unwanted side effects since overactive Hedgehog activity is linked to other diseases as well such as cancer.
Image: Washington University researchers activated the Hedgehog protein pathway in the fat cells of mice. After eight weeks of eating a high-fat diet, mice that had been engineered with genes to activate the pathway didn't gain weight (left), but control animals whose Hedgehog pathways were not activated became obese (right). Image courtesy of Washington University School of Medicine.