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Publications

Journal Article Ahead of print

PubMed: 42858701 DOI: 10.1016/j.cyto.2026.157223

Strength training attenuates hepatic inflammation and potentiates mitochondrial adaptations in IL-10-deficient mice.

Cytokine 208:157223

Authors: Driele Cassia da Silva Ferreira, Ana Paula Pinto, Macário A Rebelo, José E Tanus-Santos, Maria Eduarda A Tavares, Giovana R Teixeira, Ruither de Oliveira G Carolino, Ivo V de Sousa Neto, Fabiane Hiratsuka V de Souza, Paulo Eduardo N de Souza, José R Pauli, Dennys E Cintra, Eduardo R Ropelle, Ellen C de Freitas, Adelino S R da Silva

Affiliations

  • Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
  • School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
  • Department of Translational Medicine, State University of Campinas, Campinas, SP, Brazil. Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, SP, Brazil.
  • Multicentric Program of Postgraduate in Physiological Sciences, Sao Paulo State University (UNESP), School of Dentistry of Araçatuba, Araçatuba, Sao Paulo, Brazil.
  • Multicentric Program of Postgraduate in Physiological Sciences, Sao Paulo State University (UNESP), School of Dentistry of Araçatuba, Araçatuba, Sao Paulo, Brazil. Department of Physical Education, State University of Sao Paulo (UNESP), Presidente Prudente, Sao Paulo, Brazil.
  • Laboratory of Electron Paramagnetic Resonance, Institute of Physics, University of Brasilia, Brasilia, Brazil.
  • Laboratory of Molecular Biology of Exercise (LaBMEx), School of Applied Sciences, University of Campinas (UNICAMP), Limeira, Sao Paulo, Brazil.
  • School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. Department of Health Sciences, Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
  • Postgraduate Program in Rehabilitation and Functional Performance, Ribeirão Preto Medical School, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil. School of Physical Education and Sport of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, São Paulo, Brazil.

Abstract

The liver plays a central role in metabolic and immunological homeostasis through integrated signaling networks coordinating inflammation, mitochondrial markers, oxidative stress, nitric oxide bioavailability, and autophagy. Interleukin-10 (IL-10) is a key anti-inflammatory cytokine involved in tissue homeostasis, whereas physical exercise is a non-pharmacological strategy capable of improving mitochondrial markers and attenuating inflammation. However, whether IL-10 is required for hepatic autophagy-mitochondrial-inflammatory adaptations induced by strength training remains unclear. Here, we investigated the effects of IL-10 deficiency on hepatic mitochondrial markers, autophagic flux, inflammatory signaling, nitric oxide metabolism, and liver morphology, as well as the effects of strength training. Wild-type (WT) and IL-10 knockout (IL-10 KO) mice were allocated to sedentary or strength-trained groups for 8 weeks. Liver samples were analyzed by RT-qPCR, western blotting, electron paramagnetic resonance, chemiluminescence-based detection of nitric oxide metabolites, and histological assessment. Global IL-10 deficiency was associated with reduced liver autophagic flux and total STAT3 protein levels, together with increased hepatic inflammation and hepatic lipid volume fraction. Strength training improved physical performance in both genotypes and potentiated mitochondrial adaptations in IL-10 KO mice, including upregulation of respiratory chain complexes and bioenergetic gene expression. In IL-10 KO mice, strength training attenuated hepatic inflammation and modulated nitric oxide metabolism but did not restore autophagic flux or reduce hepatic lipid volume fraction. Exploratory bioinformatic analyses identified associations between IL-10 expression, selected autophagy-related genes, and chronic liver disease stage. Together, these findings suggest that strength training induces beneficial, but incomplete, hepatic adaptations in IL-10-deficient mice and highlight an association between IL-10 deficiency and alterations in hepatic autophagy, mitochondrial markers, and inflammatory status.

MeSH

Exercise, Genes, Autophagy, Homeostasis, Liver, Resistance Training, Biological Factors, Interleukin-10