Although it is well-documented that changes in peripheral energy metabolism produce adaptive changes in feeding behavior, there is little information regarding the brain mechanisms that link these two parameters. The experiments in this proposal are designed to address this issue. The general strategy for investigating this relationship is to: Induce alterations in energy metabolism with experimental manipulations that have been demons treated to produce reliable changes in both peripheral metabolism and feeding behavior, and measure changes in hypothalamic mechanisms known to be involved in controlling food intake. Metabolism will be manipulated acutely with metabolic inhibitors and chronically by feeding high- and low-fat diets to rats with experimental diabetes mellitus. Metabolic parameters that will be investigated include e metabolic hormones, metabolic fuel oxidation, and haptic ATP concentrations. In the hypothalamus there are transmitters that are hypothesized to be involved in the control of food intake. The central focus of this proposal will be on hypothalamic neuropeptide Y (NPY). We concentrate on NPY because it has been strongly implicated in the control of food intake, and its relationship to energy metabolism is not well understood. Changes in NPY will be assessed through measurements of NPY mRNA levels and NPY peptide content.