Ghrelin Signaling Within the Paraventricular Nucleus of the Hypothalamus Influences Sympathetic Activity But Not Brown Adipose Tissue Activity During the Stress Response

Ghrelin secretion during stress may regulate energy expenditure in the form of heat through the activation of brown adipose tissue (BAT). BAT activity involves sympathetic stimulation of non-shivering-thermogenesis through uncoupling protein-1 (UCP-1). The paraventricular nucleus of the hypothalamus (PVN) plays a role in energy expenditure by reducing sympathetic outflow on BAT. Mice were implanted with cannulae attached to osmotic minipumps delivering ghrelin receptor antagonist [D-Lys-3]-GHRP6 (20nmol/day/mouse) or vehicle by the PVN. Half of the mice were subjected to chronic social defeat stress for 19-21 days. Results showed stressed animals decreased UCP-1 expression within BAT with no drug effects. Stressed animals given the antagonist showed increased plasma norepinephrine compared to mice in other groups, but had less utilization of these in BAT. We suggest that stress alters sympathetic tone to modulate the expression of UCP-1 in BAT and these effects are not mediated by ghrelin acting on receptors in the PVN.