한빛사논문
Sang Hyeon Ju1,3, Hyeonju Yun2, Youjin Oh2, Yeeun Choi2, Jong-Woo Sohn2,4
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea
2Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea
3Present address: Department of Internal Medicine, Chungnam National University Hospital, Daejeon 35015, South Korea
4Lead contact
Corresponding author: Jong-Woo Sohn
Abstract
Melanocortin-4 receptors (MC4Rs) expressed by the central nervous system are essential regulators of energy homeostasis, and Mc4r mutation is the most common cause of human monogenic obesity. Notably, patients with obesity carrying Mc4r mutations are protected against obesity-induced hypertension, and MC4R agonists elevate blood pressure (BP). Although increased sympathetic tone by MC4Rs is suggested to underlie this phenotype, the detailed mechanisms remain unclear. Here, we investigate how MC4Rs regulate the sympathetic preganglionic neurons and find that MC4Rs activate these neurons via the protein kinase A-dependent activation of the transient receptor potential vanilloid 1 (TRPV1) channel. Importantly, we demonstrate that the inhibition of TRPV1 prevents MC4R-induced elevation of BP but does not affect MC4R-induced anorexia. We further show that TRPV1 is responsible for MC4R-dependent activation of the sympathetic preganglionic neurons by high-fat diet. Together, our results provide insight into how MC4Rs regulate sympathetic function.
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