LEIBOWITZ, SARAH F. Brain peptides and obesity: pharmacologic treatment. ObesRes. 1995;3(Supp14):573S-5893. Obesity results from an imbalance between nutrient ingestion andmetabolism,withmore calories being ingested than utilized. Thebrain plays animportant roleincoordinating these complex behavioral and physiologicalfunctions, operating through multiple neurochemical systems with distinct properties. This review focuses on two hypothalamicpeptide systems, neuropeptide Y (NPY) and galanin (GAL), that illustrate how the brain operates through different mechanisms to control the body's nutrient stores, in different states o r conditions. These peptides have different behavioralandphysiologicaleffects andare,themselves,differentially responsive to feedback signals from circulating steroids,peptides,and nutrients. They canbedistinguishedby their relation to natural feeding patterns and endogenous hormones and by their specificity of action in relation to natural biological rhythms.Theneuroanatomicalsubstrates involved in these actionsaf NPY and GAL are also distinct. The neurocircuit mediating NPY's actions originates in the arcuatenucleus and terminates in the medial portion of the paraventricular nucleus; the GAGcontaining neurons, in contrast, are concentrated in the lateral portion of the paraventricular nucleus, in addition to the medial preoptic area, which contribute to 1ocalGALinnervation as wellas projections to the median eminence. Regarding their distinct functions, the evidence suggests that the NPY system is more closely related to patterns of carbohydrate ingestion andcarbohydrate utilization, channeling nutrients towards the synthesisoffat. Itismost strongly activatedatthestartoftheactive feeding cycle or afterweaning,in close association with the adrenal steroid,corticosterone. The GAL system,in contrast, is more closely associated with patterns of fat consumption and signals related to fat oxidation. This peptide systemis most active duringthemiddleof the feeding cycle or immediately afterpuberty,in close associationwith the gonadal steroids. The gene expression and synthesis of these peptides in their respective neuronal cell groups is inhibited by circulating insulin and altered by dietary nutriFrom the Rockefeller University, New York, NY