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FASEB J. 2019 Jul;33(7):7863-7881. doi: 10.1096/fj.201802457RR. Epub 2019 Apr 2.

Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.

Author information

1
Department of Orthopedic Surgery, University of Michigan, Ann Arbor, Michigan, USA.
2
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.
3
Diabetes and Metabolism Research Center, University of Utah, Salt Lake City, Utah, USA.
4
Department of Diabetes, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
5
Department of Physiology, School of Medicine, National University of Ireland, Galway, Ireland.
6
Hospital for Special Surgery, New York, New York, USA.
7
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.

Abstract

Myosteatosis is the pathologic accumulation of lipid that can occur in conjunction with atrophy and fibrosis following skeletal muscle injury. Little is known about the mechanisms by which lipid accumulates in myosteatosis, but many clinical studies have demonstrated that the degree of lipid infiltration negatively correlates with muscle function and regeneration. Our objective was to determine the pathologic changes that result in lipid accumulation in injured muscle fibers. We used a rat model of rotator cuff injury in this study because the rotator cuff muscle group is particularly prone to the development of myosteatosis after injury. Muscles were collected from uninjured controls or 10, 30, or 60 d after injury and analyzed using a combination of muscle fiber contractility assessments, RNA sequencing, and undirected metabolomics, lipidomics, and proteomics, along with bioinformatics techniques to identify potential pathways and cellular processes that are dysregulated after rotator cuff tear. Bioinformatics analyses indicated that mitochondrial function was likely disrupted after injury. Based on these findings and given the role that mitochondria play in lipid metabolism, we then performed targeted biochemical and imaging studies and determined that mitochondrial dysfunction and reduced fatty acid oxidation likely leads to the accumulation of lipid in myosteatosis.-Gumucio, J. P., Qasawa, A. H., Ferrara, P. J., Malik, A. N., Funai, K., McDonagh, B., Mendias, C. L. Reduced mitochondrial lipid oxidation leads to fat accumulation in myosteatosis.

KEYWORDS:

fatty degeneration; muscle atrophy; muscle injury; rotator cuff

PMID:
30939247
PMCID:
PMC6593892
[Available on 2020-04-02]
DOI:
10.1096/fj.201802457RR

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