Leptin differentially regulates NPY and POMC neurons projecting to the lateral hypothalamic area

Recent studies have reinforced the view that the lateral hypothalamic area (LHA) regulates food intake and body weight. We identified leptin-sensitive neurons in the arcuate nucleus of the hypothalamus (Arc) that innervate th e LHA using retrograde tracing with leptin administration. We found that re trogradely labeled cells in the Are contained neuropeptide Y (NPY) mRNA or proopiomelanocortin (POMC) mRNA. Following leptin administration, NPY cells in the Are did not express Fos but expressed suppressor of cytokine signal ing-3 (SOCS-3) mRNA. In contrast, leptin induced both Fos and SOCS-3 expres sion in POMC neurons, many of which also innervated the LHA. These findings suggest that leptin directly and differentially engages NPY and POMC neuro ns that project to the LHA, linking circulating leptin and neurons that reg ulate feeding behavior and body weight homeostasis.