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 study have been published in Nature Medicine, and could aid development of drugs that not only prevent obesity, but also spur weight loss in people who are already overweight, said Stephen Hsu, one of the study’s corresponding authors and a principal investigator with the UF Sid Martin Biotechnology Development Institute.
Although unrelated studies have shown that lifestyle changes such as choosing healthy 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.
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.
Mice missing the TRIP-Br2 gene did not gain weight no matter what they ate, and were otherwise normal and healthy. However, 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.
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. 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.
As the studies were done mostly in mice, additional studies are still needed to see if the findings translate to humans.
‘We are very optimistic about the translational promise of our findings because we showed that only human subjects who had the kind of fat (visceral) that becomes insulin‑resistant also had high protein levels of TRIP-Br2,’ said Hsu.
‘Imagine you are able to develop drugs that pharmacologically mimic the complete absence of TRIP-Br2. If a patient started off fat, he or she would burn the weight off. If people are at risk of obesity and it’s associated conditions, it would help keep them lean regardless of how much fat they ate. That is the ideal anti-obesity drug, one that prevents obesity and helps people burn off excess weight.’