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Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism
- Source :
- Metabolomics. 12
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Older patients are more likely to acquire and die from acute respiratory distress syndrome (ARDS) and muscle weakness may be more clinically significant in older persons. 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. 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. Young (2 month), adult (6 month) and old (20 month) male C57Bl6 J 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). 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. 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.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Lung injury
Biology
Biochemistry
Article
03 medical and health sciences
chemistry.chemical_compound
Gastrocnemius muscle
0302 clinical medicine
Internal medicine
medicine
Beta oxidation
chemistry.chemical_classification
Fatty acid metabolism
Fatty acid
Muscle weakness
Skeletal muscle
respiratory system
Muscle atrophy
respiratory tract diseases
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
030220 oncology & carcinogenesis
medicine.symptom
Subjects
Details
- ISSN :
- 15733890 and 15733882
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Metabolomics
- Accession number :
- edsair.doi.dedup.....fdf62e6a3e454dadb0759b01cc3c90b7