title: Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.
abstract: The marbling of skeletal muscle by ectopic adipose tissue is a hallmark of many muscle diseases, including sarcopenia and muscular dystrophies, and generally associates with impaired muscle regeneration. Although the etiology and the molecular mechanisms of ectopic adipogenesis are poorly understood, fatty regeneration can be modeled in mice using glycerol-induced muscle damage. Using comprehensive molecular and histological profiling, we compared glycerol-induced fatty regeneration to the classical cardiotoxin (CTX)-induced regeneration model previously believed to lack an adipogenic response in muscle. Surprisingly, ectopic adipogenesis was detected in both models, but was stronger and more persistent in response to glycerol. Importantly, extensive differential transcriptomic profiling demonstrated that glycerol induces a stronger inflammatory response and promotes adipogenic regulatory networks while reducing fatty acid β-oxidation. Altogether, these results provide a comprehensive mapping of gene expression changes during the time course of two muscle regeneration models, and strongly suggest that adipogenic commitment is a hallmark of muscle regeneration, which can lead to ectopic adipocyte accumulation in response to specific physio-pathological challenges.
authors: MusculoSkeletal Diseases Group, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors: Laura
authors: L
authors: Lukjanenko
authors: Sophie
authors: S
authors: Brachat
authors: Eliane
authors: E
authors: Pierrel
authors: Estelle
authors: E
authors: Lach-Trifilieff
authors: Jerome N
authors: JN
authors: Feige
mesh_terms: D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D054715:Cardiotoxins; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D020869:Gene Expression Profiling; D005990:Glycerol; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018908:Muscle Weakness / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration / Q000235:genetics*
chemical_list: D054715:Cardiotoxins; D005227:Fatty Acids; D009124:Muscle Proteins; D005990:Glycerol
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