Abstract / Summary
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.