Characterization of adipocytes derived from fibro/adipogenic progenitors resident in human skeletal muscle

Abstract

A population of fibro/adipogenic but non-myogenic progenitors located between skeletal muscle fibers was recently discovered. The aim of this study was to determine the extent to which these progenitors differentiate into fully functional adipocytes. The characterization of muscle progenitor-derived adipocytes is a central issue in understanding muscle homeostasis. They are considered as being the cellular origin of intermuscular adipose tissue that develops in several pathophysiological situations. Here fibro/adipogenic progenitors were isolated from a panel of 15 human muscle biopsies on the basis of the specific cell-surface immunophenotype CD15+/PDGFRα+CD56−. This allowed investigations of their differentiation into adipocytes and the cellular functions of terminally differentiated adipocytes. Adipogenic differentiation was found to be regulated by the same effectors as those regulating differentiation of progenitors derived from white subcutaneous adipose tissue. Similarly, basic adipocyte functions, such as triglyceride synthesis and lipolysis occurred at levels similar to those observed with subcutaneous adipose tissue progenitor-derived adipocytes. However, muscle progenitor-derived adipocytes were found to be insensitive to insulin-induced glucose uptake, in association with the impairment of phosphorylation of key insulin-signaling effectors. Our findings indicate that muscle adipogenic progenitors give rise to bona fide white adipocytes that have the unexpected feature of being insulin-resistant.

Uncoupling protein 1 expression in adipocytes derived from skeletal muscle fibro/adipogenic progenitors is under genetic and hormonal control

“…Analysing both polyclonal and monoclonal cell cultures, we could not identify any MP subpopulation with adipogenic potential. Our results further support previous work showing that MPs are committed to the myogenic fate30, 31, 49, 51 and that FAPs are the adipocyte precursor population residing in murine30, 31, 32, 52 and human24, 51, 53, 54 adult skeletal muscle. Although we cannot reject the hypothesis that a small subpopulation of satellite cells could form brown adipocytes—as shown by Yin et al 27.…”

“…Previous studies have shown adipogenic potential for CD56 − /CD15 +, 24, 61 CD56 − /PDGFRα +, 54 or CD56 − /CD15 + /PDGFRα + 51 progenitors isolated from human skeletal muscle. These progenitors have been described to give rise to bona fide white adipocytes that are insensitive to insulin‐induced glucose uptake compared with adipocytes derived from progenitors isolated from subcutanous adipose tissue 51. In contrast, Uezumi et al 54.…”

Cardiac Fibro-Adipocyte Progenitors Express Desmosome Proteins and Preferentially Differentiate to Adipocytes Upon Deletion of the Desmoplakin Gene

“…A subset of progenitor cells in skeletal muscles, referred to as FAPs, are characterized by the expression of cell surface marker PDGFRA and exclusion of other cell types known to express PDGFRA, such as bone marrow-derived progenitors 6, 8, 24, 25 . In the heart presence and characteristics of FAPs and the subset that differentiate to adipocytes are unknown.…”

Xeno-Free Cryopreservation of Bone Marrow-Derived Multipotent Stromal Cells fromCallithrix jacchus

“…31,32 Adipsin is a mature adipocyte marker. 33 qRT-PCR analysis of adipogenic markers PPARc and adipsin revealed that there was no significant difference in PPARc expression across the frozen-thawed samples ( p > 0.05) (Fig. 4C).…”