Findings shed light on why PPARγ activators have side effect of promoting weight gain

The brain plays a central role in regulating appetite and whole-body metabolism. A protein known as PPARγ is important in the brain's control of food intake and body weight, but the identity of the neurons regulating this process has been unclear. A new study in the Journal of Clinical Investigation demonstrates that PPARγ activity in a type of neuron known as pro-opiomelanocortin (POMC) neurons is critical in mediating the response to high-fat diet.

Sabrina Diano and colleagues at Yale University School of Medicine found that mice lacking PPARγ specifically in POMC neurons gained less weight, were more active, and had improved glucose metabolism when fed a high-fat diet. Moreover, animals without PPARγ in POMC neurons did not gain weight when given PPARγ activators. The results of this study indicate that PPARγ expression in POMC neurons regulates whole-body energy balance. The findings also shed light on why PPARγ activators, which are used clinically to increase insulin sensitivity in patients with type 2 diabetes, have a side effect of promoting weight gain.