Isocitrate dehydrogenase 2 protects mice from high-fat diet-induced metabolic stress by limiting oxidative damage to the mitochondria from brown adipose tissue

Obesity: Possible protective enzyme identified An enzyme that limits the build-up of reactive oxygen species (ROS) in fat cells protects mice against metabolic stress during a high-fat diet. Calorie overload leads to high levels of damaging ROS in the mitochondria of brown fat cells. This can disrupt processes that regulate energy expenditure and glucose metabolism. A team led by Seung-Soon Im at Keimyung University, Daegu, South Korea, and Timothy F. Osborne at Johns Hopkins University, St. Petersburg, USA, examined the role of an enzyme called isocitrate dehydrogenase 2 (IDH2), which is known to regulate the build-up of mitochondrial ROS. In mice fed a high-fat diet, those without IDH2 experienced accelerated weight gain, triggered by increased ROS levels and decreased mitochondrial function. A dose of an antioxidant in the diet reduced this effect, suggesting that patients with obesity may benefit from antioxidant supplements.