[대학원 생명과학과 세미나 안내]
연사 : 손종우 교수(한국과학기술원 생명과학과)
연제 : Regulation of metabolic homeostasis by the central melanocortin system
일시 : 2022년 04월 15일 (금) 오후 4시 30분
장소 : 온라인 화상 강의로 진행됩니다.
초청교수 : 백자현 교수
Abstract
Melanocortin-4 receptors (MC4R) expressed by the neurons of the hypothalamus and the autonomic nervous system (ANS) regulate whole-body energy homeostasis. In particular, MC4Rs expressed by neurons of the paraventricular nucleus of the hypothalamus (PVH) are responsible for MC4R-induced anorexia, which serves as the neural basis for the development of novel anti-obesity drugs. Notably, it was shown that MC4R-induced inhibition of Kir7.1 channel underlie the excitation of PVH neurons. On the other hand, MC4Rs expressed by the ANS produce both beneficial and harmful effects of MC4R agonists. While the cellular mechanisms for the inhibition of parasympathetic preganglionic neurons by MC4R were identified in our previous study, those responsible for MC4R-induced excitation of sympathetic preganglionic neurons remains to be determined. In this study, we investigated the mechanisms for MC4R regulation of the sympathetic preganglionic neurons. We recorded sympathetic preganglionic neuronal activity in the spinal cord slices using whole-cell patch clamp methods, and found that MC4R agonists depolarize sympathetic preganglionic neurons via the opening of the TRPV1 channel. We also found in vivo relevance of the MC4R-TRPV1 pathway. Our results demonstrate that MC4Rs utilize distinct ion channel mechanisms in the PVH and the ANS. These findings should help to develop novel and safe anti-obesity drugs.