Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration

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...

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Published in:	PloS one 2013-08, Vol.8 (8), p.e71084
Main Authors:	Lukjanenko, Laura, Brachat, Sophie, Pierrel, Eliane, Lach-Trifilieff, Estelle, Feige, Jerome N
Format:	Article
Language:	eng
Subjects:	Adipocytes Adipocytes - metabolism Adipocytes - pathology Adipogenesis Adipogenesis - genetics Adipose tissue Adipose Tissue - metabolism Adipose Tissue - pathology Adipose tissues Analysis Animal models Animals Biology Biomedical research Cardiotoxins Diabetes Disease Models, Animal Etiology Fatty acids Fatty Acids - metabolism Gene expression Gene Expression Profiling Gene mapping Glycerin Glycerol Growth factors Health sciences Homeostasis Inflammation Inflammatory response Insulin resistance Lipid Metabolism - genetics Male Medicine Metabolism Mice Mice, Inbred C57BL Molecular modelling Muridae Muscle Proteins - genetics Muscle Proteins - metabolism Muscle Weakness - chemically induced Muscle Weakness - genetics Muscle Weakness - pathology Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscles Musculoskeletal system Myogenesis Nitrogen Oxidation Profiling Regeneration Regeneration - genetics Rodents Sarcopenia Skeletal muscle
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Summary:	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.
ISSN:	1932-6203 1932-6203