Exercise alters the circadian rhythm of REV-ERB-alpha and downregulates autophagy-related genes in peripheral and central tissues

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da Rocha, Alisson L. ; Pinto, Ana P. ; Bedo, Bruno L. S. ; Morais, Gustavo P. ; Oliveira, Luciana C. ; Carolino, Ruither O. G. ; Pauli, Jose R. ; Simabuco, Fernando M. ; de Moura, Leandro P. ; Ropelle, Eduardo R. ; Cintra, Dennys E. ; Rivas, Donato A. ; da Silva, Adelino S. R.

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 12, n. 1, p. 13-pg., 2022-11-21.

Resumo

The transcriptional repressor REV-ERB-alpha, encoded by Nuclear Receptor Subfamily 1 Group D Member 1 (Nr1d1), has been considered to play an essential role in the skeletal muscle oxidative capacity adaptation and muscle mass control. Also, this molecule regulates autophagy via the repression of autophagy-related genes both in skeletal muscle and brain regions. Classically, training programs based on endurance or strength characteristics enhance skeletal muscle mass content and/or oxidative capacity, leading to autophagy activation in several tissues. Thus, it seems that REV-ERB-alpha regulates similar responses induced by exercise. However, how this molecule responds to different exercise models/intensities in different tissues is still unclear. Therefore, the main aim was to characterize the responses of REV-ERB-alpha and autophagy-related genes to different exercise protocols (endurance/interval run/strength) in distinct tissues (gastrocnemius, soleus and hippocampus). Since REV-ERB-alpha presents a circadian rhythm, the analyses were performed in a time-course manner. The endurance and strength groups attenuated REV-ERB-alpha transcriptional response during the time course in gastrocnemius and soleus. Conversely, the interval group enhanced the Nr1d1 expression in the hippocampus. All protocols downregulated the REV-ERB-alpha protein levels in gastrocnemius following the exercise session with concomitant nuclear exclusion. The major autophagy-related genes presented downregulation after the exercise session in all analyzed tissues. Altogether, these results highlight that REV-ERB-alpha is extremely sensitive to physical exercise stimuli, including different models and intensities in skeletal muscle and the hippocampus. (AU)

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