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This Article Full Text Full Text (PDF) All Versions of this Article: 297/5/E987    most recent 00229.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Vettor, R. Articles by Federspil, G. PubMed PubMed Citation Articles by Vettor, R. Articles by Federspil, G.

Reviews

The origin of intermuscular adipose tissue and its pathophysiological implications

¹Department of Medical and Surgical Sciences, Internal Medicine 3, Metabolic Diseases and Cardiovascular Risk/Bariatric Unit, Endocrine Metabolic Laboratory, ²Department of Biomedical Sciences and ³Pediatric Surgery Division, Pediatrics Department, Padua University, Padua, Italy; ⁴Surgery Unit, University College London Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom

Submitted 6 April 2009 ; accepted in final form 23 August 2009

ABSTRACT

The intermuscular adipose tissue (IMAT) is a depot of adipocytes located between muscle bundles. Several investigations have recently been carried out to define the phenotype, the functional characteristics, and the origin of the adipocytes present in this depot. Among the different mechanisms that could be responsible for the accumulation of fat in this site, the dysdifferentiation of muscle-derived stem cells or other mesenchymal progenitors has been postulated, turning them into cells with an adipocyte phenotype. In particular, muscle satellite cells (SCs), a heterogeneous stem cell population characterized by plasticity and self-renewal that allow muscular growth and regeneration, can acquire features of adipocytes, including the abilities to express adipocyte-specific genes and accumulate lipids. Failure to express the transcription factors that direct mesenchymal precursors into fully differentiated functionally specialized cells may be responsible for their phenotypic switch into the adipogenic lineage. We proved that human SCs also possess a clear adipogenic potential that could explain the presence of mature adipocytes within skeletal muscle. This occurs under some pathological conditions (i.e., primary myodystrophies, obesity, hyperglycemia, high plasma free fatty acids, hypoxia, etc.) or as a consequence of thiazolidinedione treatment or simply because of a sedentary lifestyle or during aging. Several pathways and factors (PPARs, WNT growth factors, myokines, GEF-GAP-Rho, p66^shc, mitochondrial ROS production, PKCβ) could be implicated in the adipogenic conversion of SCs. The understanding of the molecular pathways that regulate muscle-to-fat conversion and SC behavior could explain the increase in IMAT depots that characterize many metabolic diseases and age-related sarcopenia.

muscle satellite cells; mesenchymal stem cells; myogenesis; adipogenesis