Protein key to fighting and preventing obesity identified
London: US scientists have identified a protein that, when absent, helps the body burn fat and prevents insulin resistance and obesity.
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 University of Florida Sid Martin Biotechnology Development Institute.
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."
When functioning normally, TRIP-Br2 restricts the amount of fat that cells burn as energy. But when TRIP-Br2 is absent, a fat-burning fury seems to occur in fat cells. Although other proteins have been linked to the storage and release of fat in cells, TRIP-Br2 is unique in that it regulates how cells burn fat in a few different ways, Hsu said. When TRIP-Br2 is absent, fat cells dramatically increase the release of free fatty acids and also burn fat to produce the molecular fuel called ATP that powers mitochondria — the cell``s energy source. In addition, cells free from the influence of TRIP-Br2 start using free fatty acids to generate thermal energy, which protects the body from exposure to cold.
"TRIP-Br2 is important for the accumulation of fat," said Rohit N. Kulkarni, M.D., Ph.D., also a senior author of the paper and an associate professor of medicine at Harvard Medical School and the Joslin Diabetes Center. "When an animal lacks TRIP-Br2, it can``t accumulate fat."
Because the studies were done mostly in mice, additional studies are still needed to see if the findings translate to humans.
The study was recently published online in the journal Nature Medicine.