Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.
4 affiliations
- 1School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
- 2School of Applied Sciences, University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
- 3Department of Health Sciences, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
- 4Postgraduate 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.
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BibTeX
@article{neto2026reverbα,
title = {{Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.}},
author = {Ivo Vieira de Sousa Neto and Alisson Luiz da Rocha and Ana Paula Pinto and Eliézer Lucas Pires Ramos and Eduardo Rochete Ropelle and José Rodrigo Pauli and Ellen Cristini de Freitas and Adelino Sanchez Ramos da Silva},
journal = {Journal of cellular physiology},
year = {2026},
month = oct,
doi = {10.1002/jcp.70239},
url = {https://europepmc.org/article/MED/42852640},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rev-erb-α in Skeletal Muscle Adaptation: Integrating Circadian Control Mechanisms and Exercise Dynamic Responses.
AU - Ivo Vieira de Sousa Neto
AU - Alisson Luiz da Rocha
AU - Ana Paula Pinto
AU - Eliézer Lucas Pires Ramos
AU - Eduardo Rochete Ropelle
AU - José Rodrigo Pauli
AU - Ellen Cristini de Freitas
AU - Adelino Sanchez Ramos da Silva
PY - 2026
DA - 2026/10/01
JO - Journal of cellular physiology
DO - 10.1002/jcp.70239
UR - https://europepmc.org/article/MED/42852640
AB - 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.
SN - 0021-9541
SN - 1097-4652
ER -