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Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism

Authors :
Carlos Kiyoshi Katashima
Thayana de Oliveira Micheletti
Renata Rosseto Braga
Rodrigo Stellzer Gaspar
Ludger J. E. Goeminne
Alexandre Moura-Assis
Barbara Moreira Crisol
Rafael S. Brícola
Vagner Ramon R. Silva
Camila de Oliveira Ramos
Alisson L. da Rocha
Mariana Rosolen Tavares
Fernando Moreira Simabuco
Valquiria Aparecida Matheus
Lucas Buscaratti
Henrique Marques-Souza
Patricia Pazos
David Gonzalez-Touceda
Sulay Tovar
María del Carmen García
Jose Cesar Rosa Neto
Rui Curi
Sandro Massao Hirabara
Patrícia Chakur Brum
Patrícia Oliveira Prada
Leandro P. de Moura
José Rodrigo Pauli
Adelino S. R. da Silva
Dennys Esper Cintra
Licio A. Velloso
Eduardo Rochete Ropelle
Source :
Science Advances, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
Publication Year :
2022

Abstract

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation– and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

Details

ISSN :
23752548
Database :
OpenAIRE
Journal :
Science Advances
Accession number :
edsair.doi.dedup.....978d5ee7bf61828bfbb7ed18d5ecc6d4
Full Text :
https://doi.org/10.1126/sciadv.abm7355