Type 2 diabetes and obesity are both characterized by impaired metabolic regulation and insulin resistance is a central cause in both of these conditions. Our lab studies the regulation of metabolism through the central nervous system. We employ integrated physiology approaches to deconstruct the role of the brain in orchestrating organ crosstalk such as nutrient flux between adipose tissue and the liver and its relevance in regulating insulin action. A commonly used approach in our lab is to study nutrient partitioning using metabolic tracers during clamps in rodents that allow the simultaneous assessment of lipid, glucose and amino acid fluxes. These physiological study techniques are complemented by transcriptional, proteomic and metabolomic techniques to arrive at a molecular understanding of how the brain controls nutrient fluxes in peripheral organs such as liver and adipose tissue and how in turn adipose tissue function regulates innate immunity. We have established that hypothalamic leptin and insulin signaling play important roles in the regulation of adipose tissue lipolysis and lipogenesis and are currently studying neuronal pathways that govern glucose homeostasis and lipid metabolism. In obesity and diabetes hypothalamic insulin action is impaired in part through increased endocannabinoid tone in the brain resulting in dysregulated nutrient partitioning and a pro-inflammatory state. The longterm goal of our research program is to identify therapeutic interventions that restore hypothalamic insulin action thereby improving metabolic control.