Non targeted metabolomics of gastrocnemius tissue samples obtained from 6 month old (adult) mice- Both Sham and after inducing lung injury (part II)

ABSTRACT: Introduction: Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more significant in older survivors. Recent data implicate muscle ring finger protein 1 (MuRF1) in lung injury-induced skeletal muscle atrophy in young mice and identify an alternative role for MuRF1 in cardiac metabolism regulation through inhibition of fatty acid oxidation. Objectives: To develop a model of lung injury-induced muscle wasting in old mice and to evaluate the skeletal muscle metabolomic profile of adult and old acute lung injury (ALI) mice. Methods: Young (2 month), adult (6 month) and old (20 month) male C57Bl6J mice underwent Sham (intratracheal H2O) or ALI [intratracheal E. coli lipopolysaccharide (i.t. LPS)] conditions and muscle functional testing. Metabolomic analysis on gastrocnemius muscle was performed using gas chromatography-mass spectrometry (GC-MS). Results: Old ALI mice had increased mortality and failed to recover skeletal muscle function compared to adult ALI mice. Muscle MuRF1 expression was increased in old ALI mice at day 3. Non-targeted muscle metabolomics revealed alterations in amino acid biosynthesis and fatty acid metabolism in old ALI mice. Targeted metabolomics of fatty acid intermediates (acyl-carnitines) and amino acids revealed a reduction in long chain acyl-carnitines in old ALI mice. Conclusion: This study demonstrates age-associated susceptibility to ALI-induced muscle wasting which parallels a metabolomic profile suggestive of altered muscle fatty acid metabolism. MuRF1 activation may contribute to both atrophy and impaired fatty acid oxidation, which may synergistically impair muscle function in old ALI mice.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Muscle

DISEASE(S): Lung Injury

SUBMITTER: Amro;Monte Ilaiwy;WIllis  

PROVIDER: ST000426 | MetabolomicsWorkbench | Thu Jun 30 00:00:00 BST 2016

REPOSITORIES: MetabolomicsWorkbench