University of Florida researchers and colleagues have identified a protein that, when absent, helps the body burn fat and prevents insulin resistance and obesity.
The findings from the National Institutes of Health-funded study were published online ahead of print Sunday, Jan. 6, in the journal Nature Medicine.
The discovery could aid development of drugs that not only prevent obesity, but also spur weight loss in people who are already overweight, said Stephen Hsu, M.D., Ph.D., one of the study's corresponding authors and a principal investigator with the UF Sid Martin Biotechnology Development Institute.
One-third of adults and about 17 percent of children in the United States are obese, according to the Centers for Disease Control and Prevention.
Although unrelated studies have shown that lifestyle changes such as choosing healthy food over junk food and increasing exercise can help reduce obesity, people are often unable to maintain these changes over time, Hsu said.
"The problem is when these studies end and the people go off the protocols, they almost always return to old habits and end up eating the same processed foods they did before and gain back the weight they lost during the study," he said. Developing drugs that target the protein, called TRIP-Br2, and mimic its absence may allow for the prevention of obesity without relying solely on lifestyle modifications, Hsu said.
First identified by Hsu, TRIP-Br2 helps regulate how fat is stored in and released from cells. To understand its role, the researchers compared mice that lacked the gene responsible for production of the protein, with normal mice that had the gene.
They quickly discovered that mice missing the TRIP-Br2 gene did not gain weight no matter what they ate - even when placed on a high-fat diet - and were otherwise normal and healthy. On the other hand, the mice that still made TRIP-Br2 gained weight and developed associated problems such as insulin resistance, type 2 diabetes and high cholesterol when placed on a high-fat diet. The normal and fat-resistant mice ate the same amount of food, ruling out differences in food intake as a reason why the mice lacking TRIP-Br2 were leaner.
"We had to explain why the animals eating so much fat were remaining lean and not getting high cholesterol. Where was this fat going?" Hsu said. "It turns out this protein is a master regulator. It coordinates expression of a lot of genes and controls the release of the fuel form of fat and how it is metabolized."