Acute exercise modulates Trim63 and Bmal1 in the skeletal muscle of IL-10 knockout mice

Author(s)

da Mata, Gustavo Eduardo ; Bricola, Rafael ; Ribeiro, Danielle Naves ; Simabuco, Fernando M. ; Pauli, Jose R. ; de Freitas, Ellen C. ; Ropelle, Eduardo R. ; da Silva, Adelino S. R. ; Pinto, Ana P.

• Document type: Journal article
• Source: CYTOKINE; v. 175, p. 9-pg., 2023-12-30.

Abstract

The anti-inflammatory role of physical exercise is mediated by interleukin 10 (IL-10), and their release is possibly upregulated in response to IL-6. Previous studies demonstrated that mice lacking IL-6 (IL-6 KO mice) exhibited diminished exercise tolerance, and reduced strength. Rev-erb alpha, a transcriptional suppressor involved in circadian rhythm, has been discovered to inhibit the expression of genes linked to bodily functions, encompassing inflammation and metabolism. It also plays a significant role in skeletal muscle and exercise performance capacity. Given the potential association between Rev-erb alpha and the immune system and the fact that both pathways are modulated following acute aerobic exercise, we examined the physical performance of IL-10 KO mice and analyzed the modulation of the atrophy and Rev-erb alpha pathways in the muscle of wild type (WT) and IL-10 KO mice following one session of acute exercise. For each phenotype, WT and IL-10 KO were divided into two subgroups (Control and Exercise). The acute exercise session started at 6 m/min, followed by 3 m/min increments every 3 min until animal exhaustion. Two hours after the end of the exercise protocol, the gastrocnemius muscle was removed and prepared for the reverse transcription-quantitative polymerase chain reaction (RT-q-PCR) and immunoblotting technique. In summary, compared to WT, the IL-10 KO animals showed lower body weight and grip strength in the baseline. The IL-10 control group presented a lower protein content of BMAL1. After the exercise protocol, the IL-10 KO group had higher mRNA levels of Trim63 (atrophy signaling pathway) and lower mRNA levels of Clock and Bmal1 (Rev-erb alpha signaling pathway). This is the first study showing the relationship between Rev-erb alpha and atrophy in IL-10 KO mice. Also, we accessed a public database that analyzed the gastrocnemius of MuRF KO mice submitted to two processes of muscle atrophy, a denervation surgery and dexamethasone (Dexa) injections. Independently of knockout, the denervation demonstrated lower Nr1d1 levels. In conclusion, IL-10 seems to be a determinant in the Rev-erb alpha pathway and atrophy after acute exercise, with no modulation in the baseline state. (AU)

• FAPESP's process: 21/06291-3 - Multi-user Equipament approved in grant 2019/11820-5: ChemiDoc Imaging System and accessories
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 21/08693-1 - Effect of global or conditional deletion (skeletal muscle) of the Nr1d1 gene on aging
• Grantee: Ana Paula Pinto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/11820-5 - Nr1d1 function on the aging-associated Sarcopenia
• Grantee: Adelino Sanchez Ramos da Silva
• Support Opportunities: Research Projects - Thematic Grants