Muscle Regeneration with Intermuscular Adipose Tissue (IMAT) Accumulation Is Modulated by Mechanical Constraints

Sports trauma are able to induce muscle injury with fibrosis and accumulation of intermuscular adipose tissue (IMAT), which affect muscle function. This study was designed to investigate whether hypoactivity would influence IMAT accumulation in regenerating mouse skeletal muscle using the glycerol m...

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Vydáno v:PloS one Ročník 10; číslo 12; s. e0144230
Hlavní autoři: Pagano, Allan F., Demangel, Rémi, Brioche, Thomas, Jublanc, Elodie, Bertrand-Gaday, Christelle, Candau, Robin, Dechesne, Claude A., Dani, Christian, Bonnieu, Anne, Py, Guillaume, Chopard, Angèle
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 02.12.2015
Public Library of Science (PLoS)
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ISSN:1932-6203, 1932-6203
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Shrnutí:Sports trauma are able to induce muscle injury with fibrosis and accumulation of intermuscular adipose tissue (IMAT), which affect muscle function. This study was designed to investigate whether hypoactivity would influence IMAT accumulation in regenerating mouse skeletal muscle using the glycerol model of muscle regeneration. The animals were immediately hindlimb unloaded for 21 days after glycerol injection into the tibialis anterior (TA) muscle. Muscle fiber and adipocyte cross-sectional area (CSA) and IMAT accumulation were determined by histomorphometric analysis. Adipogenesis during regenerative processes was examined using RT-qPCR and Western blot quantification. Twenty-one days of hindlimb unloading resulted in decreases of 38% and 50.6% in the muscle weight/body weight ratio and CSA, respectively, in soleus muscle. Glycerol injection into TA induced IMAT accumulation, reaching 3% of control normal-loading muscle area. This IMAT accumulation was largely inhibited in unloading conditions (0.09%) and concomitant with a marked reduction in perilipin and FABP4 protein content, two key markers of mature adipocytes. Induction of PPARγ and C/EBPα mRNA, two markers of adipogenesis, was also decreased. Furthermore, the protein expression of PDGFRα, a cell surface marker of fibro/adipogenic progenitors, was much lower in regenerating TA from the unloaded group. Exposure of regenerating muscle to hypoactivity severely reduces IMAT development and accumulation. These results provide new insight into the mechanisms regulating IMAT development in skeletal muscle and highlight the importance of taking into account the level of mechanical constraint imposed on skeletal muscle during the regeneration processes.
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Conceived and designed the experiments: AFP RD AC TB GP CD CAD. Performed the experiments: AFP RD GP TB. Analyzed the data: AFP RD GP AC AB. Contributed reagents/materials/analysis tools: AFP RD AC GP EJ CBG. Wrote the paper: AFP GP AC. Manuscript revision and feedback: AFP AC GP CD CAD RC AB.
Competing Interests: The authors have declared that no competing interests exist.
These authors also contributed equally to this work.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0144230