Summary of study ST000425

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000332. The data can be accessed directly via it's Project DOI: 10.21228/M84G7M This work is supported by NIH grant, U2C- DK119886.

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Study IDST000425
Study TitleNon targeted metabolomics of gastrocnemius tissue samples obtained from 20 month old (old) mice- Both Sham and after inducing lung injury (part I)
Study TypeNon targeted metabolomic analysis
Study SummaryIntroduction: 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.
Institute
University of North Carolina;Duke University
DepartmentUNC McAllister Heart Institute;Duke Molecular Physiology Institute
LaboratoryMultiple Centers
Last NameIlaiwy;WIllis
First NameAmro;Monte
Address111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Emailmonte_willis@med.unc.edu, amroilaiwy@gmail.com
Phone210-596-0171
Submit Date2016-06-21
Analysis Type DetailGC-MS
Release Date2016-09-23
Release Version1
Amro Ilaiwy Amro Ilaiwy
Monte WIllis Monte WIllis
https://dx.doi.org/10.21228/M84G7M
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000332
Project DOI:doi: 10.21228/M84G7M
Project Title:Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism
Project Type:Metabolomics
Project Summary:Non targeted and targeted metabolomic analysis on gastrocnemius tissue samples obtained from skeletal muscle of adult and old mice after inducing lung injury
Institute:University of North Carolina at Chapel Hill
Department:McAllister Heart Institute, Department of Internal Medicine
Laboratory:Multiple Centers
Last Name:Ilaiwy; Willis
First Name:Amro; Monte
Address:111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Email:monte_willis@med.unc.edu, amroilaiwy@gmail.com
Phone:210-596-0171
Funding Source:NIH, Fondation Leducq, Claude D. Pepper Older Americans Independence Center, the American Thoracic Society Foundation
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