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FASEB J ; 33(7): 7863-7881, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30939247

RESUMO

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.


Assuntos
Tecido Adiposo/metabolismo , Metabolismo dos Lipídeos , Mitocôndrias Musculares/metabolismo , Transtornos Musculares Atróficos/metabolismo , Lesões do Manguito Rotador/patologia , Tecido Adiposo/patologia , Animais , Colágeno/análise , Perfilação da Expressão Gênica , Ontologia Genética , Lipidômica , Masculino , Metabolômica , Contração Muscular , Denervação Muscular , Transtornos Musculares Atróficos/genética , Transtornos Musculares Atróficos/patologia , Oxirredução , Análise de Componente Principal , Proteômica , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Lesões do Manguito Rotador/metabolismo , Análise de Sequência de RNA
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