Emerging role of rev-erb-α in molecular adaptations to different physical exercise models

Author(s)

Alisson Luiz da Rocha

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2022-04-04

Examining board members

Adelino Sanchez Ramos da Silva; Ismael Forte Freitas Junior

• Advisor: Adelino Sanchez Ramos da Silva

Abstract

Recently, the nuclear receptor rev-erb-&alpha; has been considered to play an important role in the skeletal muscle oxidative capacity adaptation, modulating the AMP-activated protein kinase (AMPK) signaling pathway. Classically, endurance physical exercise is able to activate this signaling pathway, but the effects of this and other physical exercise models (i.e., resistance and exhaustive) on rev-erb-&alpha; remain unknown. Besides the transcriptional regulation of this signaling pathway, rev-erb-&alpha; is also capable to regulate negatively the autophagy pathway in skeletal muscle and the dopamine biosynthesis in hippocampus. It is suggested in the literature that dopamine, together with serotonin, play a role in cognitive fatigue development. Briefly, rev-erb-&alpha; is candidate to modulate the molecular adaptations that regulate physical performance, CNS fatigue and autophagy. Thus, the main aim of the present thesis was to investigate the role of rev-erb-&alpha; in the molecular adaptations that regulate physical performance, CNS fatigue and autophagy after different exercise models. Mice were divided as follow: into 1 control group (CT, sedentary) and 4 groups to acute exercise endurance (END, submitted to continuous aerobic physical exercise protocol), interval (INT, submitted to interval aerobic exercise protocol), strength (FOR, submitted to strength physical exercise protocol) and exhaustive (EX; submitted to exhaustive running protocol); 1 group for chronic exercise training - overtraining (OT) and 1 sedentary group (SED). The following methodologies were used: immunoblotting, real-time polymerase chain reaction (qPCR) and ELISA. The level of significance of p < 0.05 was adopted. In general, Rev-erb-&alpha; was extremely sensitive to physical exercise stimuli, including different models, intensities and volumes, both in skeletal muscle and in the hippocampus. In addition, this molecule showed adaptations in responses to overtraining, suggesting that it may participate in the development of the NFOR state. The kynurenine (KYN) pathway was also sensitive to the exhaustive physical exercise session, showing a shift to a neurotoxic metabolite production profile in the gastrocnemius. Interestingly, an inedited relationship between Rev-erb-&alpha; and the KYN pathway was evidenced. Therefore, Rev-erb-&alpha; shows as an important molecule with several actions in molecular adaptations to different models of physical exercise. (AU)

• FAPESP's process: 17/12765-2 - Emerging role of rev-erb-alpha in molecular adaptations to different physical exercise models
• Grantee: Alisson Luiz da Rocha
• Support Opportunities: Scholarships in Brazil - Doctorate