Neuropeptide Y signaling from the hypothalamus inhibits sympathetic outflow to brown adipose tissue through GABA inhibition of the rostral medullary raphe (1126.8)

Abstract

The arcuate nucleus is a central area involved in the regulation of metabolic thermogenesis in peripheral organs including brown adipose tissue (BAT). However, the efferent pathways from this nucleus for metabolic regulation are unknown. Activation of neuropeptide Y (NPY) neurons in the arcuate nucleus results in lowered metabolism likely through their direct projection to the paraventricular hypothalamic nucleus (PVH). In this study, we tested the hypothesis that NPY‐triggered neural signaling from the PVH inhibits sympathetic premotor neurons in the rostral medullary raphe (rMR) that control BAT thermogenesis. Sympathetic nerve activity and temperature in interscapular BAT were recorded in anesthetized rats, whose trunk was covered with a water jacket to control the skin temperature. Skin cooling‐evoked increase in BAT thermogenesis was eliminated by injection of NPY into the lateral ventricle or PVH. NPY injection into the PVH also eliminated BAT thermogenesis evoked by glutamate receptor stimulation in the rMR with an NMDA nanoinjection. On the other hand, NPY injection into the PVH did not affect BAT thermogenesis evoked by antagonizing GABA receptors in the rMR with a bicuculline injection. These results suggest that NPY signaling from the PVH activates a GABAergic inhibitory drive to sympathetic premotor neurons in the rMR to attenuate BAT themogenesis, leading to reduced energy expenditure.Grant Funding Source: Supported by NEXT Program and by Grants‐in‐Aid for Scientific Research, MEXT, Japan