Arrighi N, Moratal C, Clément N, Giorgetti-Peraldi S, Peraldi P, Loubat A, Kurzenne J-Y, Dani C, Chopard A, Dechesne C A
1] UFR Sciences, Université Nice Sophia Antipolis, Nice F-06108, France [2] CNRS, UMR7277, F-06108 Nice, France [3] INSERM U1091, F-06108 Nice, France.
1] UFR Sciences, Université Nice Sophia Antipolis, Nice F-06108, France [2] INSERM U 1065, Mediterranean Research Centre for Molecular Medicine, Team: Cellular and Molecular Physiopathology of Obesity and Diabetes, Nice, France.
Cell Death Dis. 2015 Apr 23;6(4):e1733. doi: 10.1038/cddis.2015.79.
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.
最近发现了一群位于骨骼肌纤维之间的成纤维/脂肪生成但非肌源性祖细胞。本研究的目的是确定这些祖细胞分化为功能完全成熟的脂肪细胞的程度。肌肉祖细胞衍生的脂肪细胞的特性是理解肌肉内环境稳定的核心问题。它们被认为是在几种病理生理情况下发展起来的肌间脂肪组织的细胞起源。在这里，基于特定的细胞表面免疫表型CD15+/PDGFRα+CD56-，从15例人类肌肉活检样本中分离出成纤维/脂肪生成祖细胞。这使得对它们向脂肪细胞的分化以及终末分化脂肪细胞的细胞功能进行研究成为可能。发现脂肪生成分化受与调节来自白色皮下脂肪组织的祖细胞分化相同的效应器调控。同样，基本的脂肪细胞功能，如甘油三酯合成和脂肪分解，其发生水平与皮下脂肪组织祖细胞衍生的脂肪细胞所观察到的水平相似。然而，发现肌肉祖细胞衍生的脂肪细胞对胰岛素诱导的葡萄糖摄取不敏感，这与关键胰岛素信号效应器磷酸化的受损有关。我们的研究结果表明，肌肉脂肪生成祖细胞产生了真正的白色脂肪细胞，这些脂肪细胞具有意想不到的胰岛素抵抗特征。
