Melanocortin-4 receptors activate sympathetic preganglionic neurons and elevate blood pressure via TRPV1.
Cell Rep
; 41(5): 111579, 2022 11 01.
Article
em En
| MEDLINE
| ID: mdl-36323255
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor Tipo 4 de Melanocortina
/
Obesidade
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Coréia do Sul