Short‐chain fatty acids activate sympathetic neurons via a novel signaling pathway

Abstract

Mammals maintain energy homeostasis by regulating sympathetic nervous system. We previously reported that GPR41, a Gi/o‐protein coupled receptor for short‐chain fatty acids (SCFAs), directly regulate sympathetic activity and energy expenditure at the level of ganglion (1). However, the signaling mechanism for GPR41‐mediated sympathetic activation in details remains to be elucidated. In this study, we examined the downstream signaling of GPR41 for sympathetic activation using primary‐cultured mouse sympathetic neurons. SCFA propionate increased tritium‐labeled noradrenaline secretion via GPR41. Pharmacological and RNAi experiments showed that propionate‐induced increase of noradrenaline secretion is mediated by Gβγ‐PLCβ3‐ERK1/2 pathway. Moreover, co‐immunoprecipitation experiments showed that activated ERK1/2 phosphorylates synapsin2, synaptic vesicle‐associated protein. Furthermore, siRNA for synapsin2 effectively suppressed propionate‐induced noradrenaline secretion. The results show a novel signaling mechanism for Gai/o‐coupled receptor GPR41‐promoted noradrenaline secretion from sympathetic nerve.This study was supported by research grants from the Japan Science and Technology Agency.