Tissue Specific Inhibition of Diet-Induced Thermogenesis

Our objective is to determine the specific roles of white adipose tissue, brown adipose tissue and muscle in diet-induced thermogenesis. We will test the hypothesis that adrenergic signaling in muscle is required for thermogenic adaptations to high fat diet. While our hypothesis focuses on muscle as the central thermogenic organ in response to increased calories, this application will test the roles of white, brown adipose tissue and muscle in mediating the thermogenic/adrenergic response to overnutrition. To do this we will utilize new technologies where adrenergic signaling can be specifically and acutely ablated in a cell specific manner. We will utilize transgenic, tissue-specific expression of DREADD receptors, coupled to the inhibitory heterotrimeric G protein Gi.