Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Cell Stem Cell. 2021 Apr 1;28(4):702-717.e8. doi: 10.1016/j.stem.2021.01.002. Epub 2021 Feb 3.
The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism. Reducing the mitochondrial β-oxidative capacity of PDGFRβ+ cells via inducible expression of MitoNEET drives a pro-inflammatory phenotype in adipose progenitors and alters lineage commitment. Furthermore, disrupting mitochondrial function in PDGFRβ+ cells rapidly induces alterations in immune cell composition in lean mice and impacts expansion of adipose tissue in diet-induced obesity. The adverse effects on adipose tissue remodeling can be reversed by restoring mitochondrial activity in progenitors, suggesting therapeutic potential for targeting energy metabolism in these cells.
脂肪组织基质是分子上不同的干细胞和祖细胞群体的丰富来源，这些细胞群体在代谢调节、脂肪生成和炎症中具有多种功能。然而，这些群体的本体论以及控制它们对刺激（如过度喂养）反应的机制尚不清楚。在这里，我们表明，脂肪血小板衍生生长因子受体 β (PDGFRβ) +祖细胞亚群的发育命运和功能特性受到线粒体代谢的严格调节。通过诱导表达 MitoNEET 降低 PDGFRβ+细胞的线粒体 β-氧化能力，可在脂肪祖细胞中驱动促炎表型，并改变谱系分化。此外，在 lean 小鼠中破坏 PDGFRβ+细胞的线粒体功能会迅速改变免疫细胞组成，并影响饮食诱导肥胖小鼠的脂肪组织扩张。通过在祖细胞中恢复线粒体活性可以逆转对脂肪组织重塑的不利影响，这表明靶向这些细胞的能量代谢具有治疗潜力。
