title: Muscle Regeneration with Intermuscular Adipose Tissue (IMAT) Accumulation Is Modulated by Mechanical Constraints.
abstract: 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.
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Allan F
authors.initials: AF
authors.lastname: Pagano
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Demangel
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brioche
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Jublanc
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Bertrand-Gaday
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Robin
authors.initials: R
authors.lastname: Candau
authors.affiliation: Université Nice-Sophia Antipolis, iBV, CNRS UMR7277, INSERM U1091, 06107, Nice, France.
authors.forename: Claude A
authors.initials: CA
authors.lastname: Dechesne
authors.affiliation: Université Nice-Sophia Antipolis, iBV, CNRS UMR7277, INSERM U1091, 06107, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Bonnieu
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Py
authors.affiliation: Université de Montpellier, INRA, UMR866 Dynamique Musculaire et Métabolisme, F-34060, Montpellier, France.
authors.forename: Angèle
authors.initials: A
authors.lastname: Chopard
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D019417:Hindlimb Suspension / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D047495:PPAR gamma; D012333:RNA, Messenger