Increasing plasma L-kynurenine impairs mitochondrial oxidative phosphorylation prior to the development of atrophy in murine skeletal muscle: A pilot study

• DOI: 10.3389/fphys.2022.992413
• Publication Date: 2022-09-30T12:26:37Z
• Authors: Victoria R. Palzkill; Trace Thome; Ania L. Murillo; Ram B. Khattri; Terence E. Ryan
• Keywords: Muscle Atrophy

Introduction: L-Kynurenine (L-Kyn), a product of tryptophan (Trp) catabolism, has been linked with impairments in walking speed, muscle strength/size, and physical function. The purpose this pilot study was to develop dietary model that elevates plasma L-Kyn levels mice characterize its impact on health Methods: Four-month-old C57BL6J male were randomized either supplemented (150 mg/kg) or chow diet for 10 weeks. Plasma Trp measured via mass spectrometry. Primary outcomes included assessments weights, myofiber cross-sectional area (CSA), nerve-stimulated contractile performance, mitochondrial oxidative phosphorylation (OXPHOS) hydrogen peroxide (H2O2) production. Additional experiments cultured myotubes explored the enhancing metabolism. Results: Mice displayed significant increases (p = 0.0028) L-Kyn/Trp ratio 0.011) when compared fed mice. Food intake body weights not different between groups. There no detectable differences CSA, performance. reductions OXPHOS 0.05) maximal ADP-stimulated respiration 0.0498). In myotubes, overexpression peroxisome proliferator-activated receptor-gamma coactivator 1 alpha prevented atrophy proteolysis, as well deficits treatment. Conclusion: Dietary feeding healthy Mitochondrial observed elevated without changes size Enhancing metabolism can protect against these effects culture myotubes.