Journal Article Review Ppublish
PubMed: 42852640 DOI: 10.1002/jcp.70239
Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.
J Cell Physiol 241(10):e70239
Authors: Ivo Vieira de Sousa Neto, Alisson Luiz da Rocha, Ana Paula Pinto, Eliézer Lucas Pires Ramos, Eduardo Rochete Ropelle, José Rodrigo Pauli, Ellen Cristini de Freitas, Adelino Sanchez Ramos da Silva
Affiliations
- School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
- School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
- Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
- Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
Abstract
Circadian rhythms orchestrate a host of biological processes in a time-dependent manner to maintain homeostasis in response to exercise. Within this framework, Rev-erb-α, an intracellular nuclear receptor and transcriptional regulator, transcends its role in circadian rhythms to drive myogenesis, muscle remodeling, primary metabolism, and autophagy, underscoring its versatile, pleiotropic actions. This review consolidates experimental evidence from cell culture, genetically modified animal models, drug-based approaches and humans, highlighting the role of Rev-erb-α mechanisms in skeletal muscle and exercise adaptation. Recent frontier-of-knowledge data indicate that acute and chronic exercise elicit distinct Rev-erb-α signatures. There is bimodal regulation: Rev-erb-α is downregulated immediately post-exercise, followed by a subsequent increase, reflecting its primary role in pathway repression. In chronic conditions, the upregulation of Rev-erb-α can act as an adaptive mechanism that governs robust responses to energy demand and mitochondrial function, thereby coordinating the metabolic network, calcium homeostasis, and oxidative capacity. Also, Rev-erb-α overexpression or its pharmacological activation may reduce pathways associated with muscle atrophy, thereby preserving tissue function and muscle mass. Excitingly, higher physical activity levels increase the amplitude of Rev-erb-α over 24 h, enhancing health and performance. However, exercise timing determines the Rev-erb-α signature that affects downstream phenotypes in skeletal muscle. Thus, elucidating the mechanisms of regulation and action of the Rev-erb-α protein may offer new perspectives for improving or preserving muscle quality across different health conditions and diseases.
MeSH
Exercise, Cells, Autophagy, Muscles, Circadian Rhythm, Homeostasis, Cell Biology, Muscle, Skeletal