A Brain-Melanocortin-Vagus axis mediates adipose tissue expansion independently of energy intake.

The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing Sympathetic Nervous input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here we demonstrate that obesogenic signals, including reduction of brain-melanocortin signaling or high-fat feeding, actively promote fat mass gain independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. These signals promote adipose tissue expansion by activating lipogenic program and adipocyte and endothelial cell proliferation independently of insulin action or the sympathetic tone to adipose tissue. These data reveal a novel physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity. This experiment involves a 2 x 2 design (Subdiaphragmatic Vagotomy x icv infusion of SHU9119) with 4 replicates per group (16 samples total).