Abstract
Chronic inflammation (CI) can contribute to muscle atrophy and sarcopenia. Resistance exercise (RE) promotes increased and/or maintenance of skeletal muscle mass, but the effects of RE in the presence of CI are unclear. In this study, we developed a novel animal model of CI-induced muscle atrophy and examined the effect of acute or chronic RE by electrical stimulation. CI was induced in young female Lewis rats by injection with peptidoglycan-polysaccharide (PG-PS). Extracellular signal-regulated kinase (ERK), p70S6 kinase (p70S6K), 4E binding protein 1 (4E-BP1), Akt, and Forkhead box O1 (FOXO1) phosphorylation levels increased in gastrocnemius (Gas) muscle from normal rats subjected to acute RE. After acute RE in CI rats, increased levels of phosphorylated ERK, p70S6K, and 4E-BP1, but not Akt or FOXO1, were observed. Chronic RE significantly increased the Gas weight in the exercised limb relative to the nontrained opposing limb in CI rats. Dietary supplementation with anti-inflammatory agents, eicosapentaenoic/docosahexaenoic acid and α-lactalbumin attenuated CI-induced muscle atrophy in the untrained Gas and could promote RE-induced inhibition of atrophy in the trained Gas. In the trained leg, significant negative correlations (r ≤ -0.80) were seen between Gas weights and CI indices, including proinflammatory cytokines and white blood cell count. These results indicated that the anabolic effects of RE are effective for preventing CI-induced muscle atrophy but are partially attenuated by inflammatory molecules. The findings also suggested that anti-inflammatory treatment together with RE is an effective intervention for muscle atrophy induced by CI. Taken together, we conclude that systemic inflammation levels are associated with skeletal muscle protein metabolism and plasticity.NEW & NOTEWORTHY This study developed a novel chronic inflammation (CI) model rat demonstrating that resistance exercise (RE) induced activation of protein synthesis signaling pathways and mitigated skeletal muscle atrophy. These anabolic effects were partially abrogated likely through attenuation of Akt/Forkhead box O1 axis activity. The degree of skeletal muscle atrophy was related to inflammatory responses. Dietary supplementation with anti-inflammatory agents could enhance the anabolic effect of RE. Our findings provide insight for development of countermeasures for CI-related muscle atrophy, especially secondary sarcopenia.