title: The origin of intermuscular adipose tissue and its pathophysiological implications.
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.
authors.affiliation: Dept. of Medical and Surgical Sciences, Univ. of Padua, via Ospedale, 105, 35128 Padua, Italy. roberto.vettor@unipd.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Vettor
authors.forename: Gabriella
authors.initials: G
authors.lastname: Milan
authors.forename: Chiara
authors.initials: C
authors.lastname: Franzin
authors.forename: Marta
authors.initials: M
authors.lastname: Sanna
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Federspil
mesh_terms: D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000254:growth & development* / Q000503:physiopathology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005819:Genetic Markers; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008931:Mitochondria, Muscle / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D009132:Muscles / Q000503:physiopathology; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D005819:Genetic Markers; D051153:Wnt Proteins