Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism

D. Clark Files, Amro Ilaiwy, Traci L. Parry, Kevin W. Gibbs, Chun Liu, James R. Bain, Osvaldo Delbono, Michael J. Muehlbauer, Monte Willis

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction: 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. 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 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). 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.

Original languageEnglish (US)
Article number134
JournalMetabolomics
Volume12
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

Lung Injury
Metabolism
Acute Lung Injury
Muscle
Skeletal Muscle
Fatty Acids
Muscles
Metabolomics
Fingers
Carnitine
Proteins
Amino Acids
Muscular Atrophy
Muscle Weakness
Adult Respiratory Distress Syndrome
Gas Chromatography-Mass Spectrometry
Enzyme inhibition
Atrophy
Lipopolysaccharides
Oxidation

Keywords

  • Acute respiratory distress syndrome
  • Aging
  • Fatty acid metabolism
  • Intensive care unit acquired weakness
  • Metabolomics
  • MuRF1
  • Muscle atrophy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry

Cite this

Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism. / Files, D. Clark; Ilaiwy, Amro; Parry, Traci L.; Gibbs, Kevin W.; Liu, Chun; Bain, James R.; Delbono, Osvaldo; Muehlbauer, Michael J.; Willis, Monte.

In: Metabolomics, Vol. 12, No. 8, 134, 01.08.2016.

Research output: Contribution to journalArticle

Files, DC, Ilaiwy, A, Parry, TL, Gibbs, KW, Liu, C, Bain, JR, Delbono, O, Muehlbauer, MJ & Willis, M 2016, 'Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism', Metabolomics, vol. 12, no. 8, 134. https://doi.org/10.1007/s11306-016-1079-5
Files, D. Clark ; Ilaiwy, Amro ; Parry, Traci L. ; Gibbs, Kevin W. ; Liu, Chun ; Bain, James R. ; Delbono, Osvaldo ; Muehlbauer, Michael J. ; Willis, Monte. / Lung injury-induced skeletal muscle wasting in aged mice is linked to alterations in long chain fatty acid metabolism. In: Metabolomics. 2016 ; Vol. 12, No. 8.
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abstract = "Introduction: 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. 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 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). 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.",
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AU - Files, D. Clark

AU - Ilaiwy, Amro

AU - Parry, Traci L.

AU - Gibbs, Kevin W.

AU - Liu, Chun

AU - Bain, James R.

AU - Delbono, Osvaldo

AU - Muehlbauer, Michael J.

AU - Willis, Monte

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N2 - Introduction: 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. 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 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). 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.

AB - Introduction: 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. 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 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). 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.

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KW - Aging

KW - Fatty acid metabolism

KW - Intensive care unit acquired weakness

KW - Metabolomics

KW - MuRF1

KW - Muscle atrophy

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