Abstract 2201 Lipidomic and metabolomic response of skeletal muscle to short term disuse atrophy in middle-aged adults

Introduction Research on muscle disuse has primarily focused on the mechanisms underlying the regulation of muscle cell atrophy. The utilization of a modern 'omics' approach allows for a more extensive assessment of how skeletal muscle metabolism may contribute to disuse atrophy and reduced function. Methods Healthy, middle-aged adults (n=11; 57.1±1.5y; BMI 28.9±1.5kg·m-2; 6m, 5f) underwent 7 days of unilateral leg immobilization via unilateral lower limb suspension (ULLS). Muscle biopsies from the m vastus lateralis of the immobilized (IMM) were collected prior to and following immobilization. We used a targeted lipidomic and metabolomic approach to determine the effects of disuse atrophy on lipid molecular species and polar metabolites in skeletal muscle. Results A total of 960 individual lipids and 205 polar metabolites were identified. A paired samples t-test showed that after 7 days of unilateral leg immobilization 39 lipid molecular species and 3 polar metabolites were significantly increased, in contrast 9 lipid molecular species and 24 polar metabolites were significantly reduced (fold change > 2, P<0.05) in the IMM leg. Of these 39 lipid species that were elevated, 27 were phosphatidylglycerols and phosphatidylinositols. Pathway analysis found significant differences after immobilization. Amino acid metabolism, particularly phenylalanine, tyrosine and tryptophan metabolism pathways were significantly altered after disuse (P<0.05). More specifically metabolites in the arginine and glutamate metabolism pathway were less abundant after disuse (P<0.05). Conclusions Short-term muscle disuse atrophy in middle-aged humans increases specific lipid species (e.g., phosphatidylinositols and phosphatidylglycerols) while reducing pathways linked to specific amino acid metabolism (e.g., glutamate and arginine). Supported by: National Institute on Aging (NIA R01AG064386), The Claude D. Pepper Older Americans Independence Center (NIA P30AG071150), Aging and Institute for Translational Sciences-Clinical Research Center (NIH UL1TR001439).