Effects of short-term endurance and strength exercise in the molecular regulation of skeletal muscle in hyperinsulinemic and hyperglycemic Slc2a4(+/-) mice

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Munoz, Vitor Rosetto ; Botezelli, Jose Diego ; Gaspar, Rafael Calais ; da Rocha, Alisson L. ; Vieira, Renan Fudoli Lins ; Crisol, Barbara Moreira ; Braga, Renata Rosseto ; Severino, Matheus Brandemarte ; Nakandakari, Susana Castelo Branco Ramos ; Antunes, Gabriel Calheiros ; Brunetto, Sergio Q. ; Ramos, Celso D. ; Velloso, Licio Augusto ; Simabuco, Fernando Moreira ; de Moura, Leandro Pereira ; da Silva, Adelino Sanchez Ramos ; Ropelle, Eduardo Rochete ; Cintra, Dennys Esper ; Pauli, Jose Rodrigo

• Document type: Journal article
• Source: CELLULAR AND MOLECULAR LIFE SCIENCES; v. 80, n. 5, p. 16-pg., 2023-05-01.

Abstract

ObjectiveIntriguingly, hyperinsulinemia, and hyperglycemia can predispose insulin resistance, obesity, and type 2 diabetes, leading to metabolic disturbances. Conversely, physical exercise stimulates skeletal muscle glucose uptake, improving whole-body glucose homeostasis. Therefore, we investigated the impact of short-term physical activity in a mouse model (Slc2a4(+/-)) that spontaneously develops hyperinsulinemia and hyperglycemia even when fed on a chow diet.MethodsSlc2a4(+/-) mice were used, that performed 5 days of endurance or strength exercise training. Further analysis included physiological tests (GTT and ITT), skeletal muscle glucose uptake, skeletal muscle RNA-sequencing, mitochondrial function, and experiments with C2C12 cell line.ResultsWhen Slc2a4(+/-) mice were submitted to the endurance or strength training protocol, improvements were observed in the skeletal muscle glucose uptake and glucose metabolism, associated with broad transcriptomic modulation, that was, in part, related to mitochondrial adaptations. The endurance training, but not the strength protocol, was effective in improving skeletal muscle mitochondrial activity and unfolded protein response markers (UPRmt). Moreover, experiments with C2C12 cells indicated that insulin or glucose levels could contribute to these mitochondrial adaptations in skeletal muscle.ConclusionsBoth short-term exercise protocols were efficient in whole-body glucose homeostasis and insulin resistance. While endurance exercise plays an important role in transcriptome and mitochondrial activity, strength exercise mostly affects post-translational mechanisms and protein synthesis in skeletal muscle. Thus, the performance of both types of physical exercise proved to be a very effective way to mitigate the impacts of hyperglycemia and hyperinsulinemia in the Slc2a4(+/-) mouse model. (AU)

• FAPESP's process: 16/18488-8 - The role of physical exercise on molecular pathways of glucose uptake in GLUT-4 knockout mice
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/26000-2 - The role of Rock protein on glucose uptake in the skeletal muscle of exercised rodents during the aging process
• Grantee: Vitor Rosetto Muñoz
• Support Opportunities: Scholarships in Brazil - Master
• 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
• FAPESP's process: 20/13443-1 - Implications of aerobic exercise on the Notch 1 signaling pathway and regulation of lipogenesis and gluconeogenesis in the liver
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/20872-6 - Effects of physical exercise on Rock protein signaling pathway, and lipogenic regulation and gluconeogenesis in the liver of aged rats
• Grantee: José Rodrigo Pauli
• Support Opportunities: Regular Research Grants