Hypothalamic neuronal targets of leptin. Leptin inhibits feeding and increases energy expenditure by directly suppressing neuropeptide Y (NPY) and increasing proopiomelanocortin (POMC). Neurons in the arcuate nucleus expressing these peptides project to the paraventricular nucleus and lateral hypothalamic area, resulting in increases in CRH and TRH and reductions in melanin-concentrating hormone (MCH) and orexins. The net effect of leptin is to suppress appetite, reduce weight, and enhance fatty acid oxidation and insulin sensitivity in peripheral organs. AGRP, Agouti-related peptide; LRb, long leptin receptor; MC4R, melanocortin 4 receptor; MSH, melanin-stimulating hormone; TG, triglycerides.