Muscle regeneration with intermuscular adipose tissue (IMAT) accumulation is modulated by mechanical constraints

Allan Pagano (1) , Rémi Demangel (1) , Thomas Brioche (2) , Elodie Jublanc (1) , Christelle Bertrand-Gaday (1) , Robin Candau (2) , Claude A. Dechesne (3, 4) , Christian Dani (3, 4) , Anne Bonnieu (1) , Guillaume Py (1) , Angèle Chopard (1)

1 DMEM - Dynamique Musculaire et Métabolisme
2 UMR SELMET - Systèmes d'élevage méditerranéens et tropicaux
3 IBV - Institut de Biologie Valrose
4 INSERM - Institut National de la Santé et de la Recherche Médicale

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.

Mots clés: muscle; regénération musculaire

Domaines: Sciences du Vivant [q-bio]

Allan Pagano, Rémi Demangel, Thomas Brioche, Elodie Jublanc, Christelle Bertrand-Gaday, et al.. Muscle regeneration with intermuscular adipose tissue (IMAT) accumulation is modulated by mechanical constraints. PLoS ONE, 2015, 10 (12), ⟨10.1371/journal.pone.0144230⟩. ⟨hal-01837620⟩