Mechanism turns white fat to energy-burning brown fat

Columbia University Medical Centre (CUMC) researchers have identified a mechanism that can give energy-storing white fat some of the beneficial characteristics of energy-burning brown fat. The findings, based on studies of mice and of human fat tissue, could lead to new strategies for treating obesity and type 2 diabetes. The study was published today in the online edition of the journal Cell.

Humans have two types of fat tissue: white fat, which stores excess energy in the form of triglycerides, and brown fat, which is highly efficient at dissipating stored energy as heat. Newborns have a relative abundance of brown fat, as protection against exposure to cold temperatures. In adults, however, almost all excess energy is stored as white fat.

''Turning white fat into brown fat is an appealing therapeutic approach to staunching the obesity epidemic, but it has been difficult to do so in a safe and effective way,'' said study leader Domenico Accili, MD, professor of Medicine and the Russell Berrie Foundation Professor at CUMC.

White fat can be ''browned'' with a class of drugs called thiazolidazines (TZDs), which increase the body's sensitivity to insulin. However, TZDs have many adverse effects - including liver toxicity, bone loss, and, ironically, weight gain - which have limited the use of these drugs.

The current study was undertaken to learn more about the function of TZDs, with the ultimate goal of developing better ways to promote the browning of white fat.

Scientists have known that TZDs promote the browning of white fat by activating a cell receptor called peroxisome proliferator-activated receptor–gamma (ppar-gamma), but the exact mechanism was not clear. To learn more, Dr. Accili and his colleagues studied a group of enzymes called sirtuins, which are thought to affect various biological processes, including metabolism.