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Understanding How Neurons Regulate Metabolism in Response to a High-Fat Diet

The brain plays a central role in regulating appetite and whole-body metabolism. A protein known as PPARgamma 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 published online on August 1, 2014 in the Journal of Clinical Investigation demonstrates that PPARgamma activity in a type of neuron known as pro-opiomelanocortin (POMC) neurons is critical in mediating the response to high-fat diet. Sabrina Diano, Ph.D., 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 PPARgamma in POMC neurons did not gain weight when given PPARgamma activators. The results of this study indicate that PPARgamma expression in POMC neurons regulates whole-body energy balance. The findings also shed light on why PPARgamma activators, which are used clinically to increase insulin sensitivity in patients with type 2 diabetes, have a side effect. Image shows PPAR gamma bound to DNA. [Press release] [Journal of Clinical Investigation article]