My research focuses on hypothalamic mechanisms sensing nutrients availability and hormonal milieu in the regulation of metabolism. The hypothalamus plays a major role in the regulation of energy homeostasis by integrating hormonal and nutritional signals. An increasing amount of evidence supports the idea that specific neurons in the hypothalamus acutely respond to changing glucose, lipid and amino acid levels. However, the intracellular substrate for such “fuel-sensing” and its integration with the hormonal status in the regulation of neuronal functions that relate to regulation of whole body energy homeostasis remains elusive. Evidences from my laboratory point to differential fuel utilization, free radical formation and uncoupling proteins as critical components in the regulation of neuronal functions. Furthermore, we have been interested in the role of peptidases in the hypothalamic regulation of energy metabolism. Specifically we showed that Prolyl carboxypeptidase is the enzyme responsible for the degradation of alpha-melanocyte stimulating hormone, a major anorexigenic neuropeptide. The results of my research have implication for understanding the pathogenesis of metabolic disorders such as obesity and type 2 diabetes, a leading cause of morbidity and mortality in the US.