Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue.
Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue.
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DOI：
10.1016/j.stem.2021.01.002
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发表时间：
2021-04-01
期刊：
影响因子：
23.9
通讯作者：
Scherer PE
中科院分区：
文献类型：
--
作者：
Joffin N;Paschoal VA;Gliniak CM;Crewe C;Elnwasany A;Szweda LI;Zhang Q;Hepler C;Kusminski CM;Gordillo R;Oh DY;Gupta RK;Scherer PE
脂肪组织基质是分子上不同的干细胞和祖细胞群的丰富来源，在代谢调节、脂肪生成和炎症方面具有多种功能。然而，这些种群的本体论以及控制它们响应过度喂养等刺激的行为的机制尚不清楚。在这里，我们表明脂肪 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 MitoNEET 的诱导表达降低 PDGFRβ+ 细胞的线粒体 β-氧化能力可驱动脂肪祖细胞中的促炎表型并改变谱系定向。此外，破坏 PDGFRβ+ 细胞中的线粒体功能会迅速诱导瘦小鼠免疫细胞组成的改变，并影响饮食引起的肥胖症中脂肪组织的扩张。通过恢复祖细胞中的线粒体活性可以逆转对脂肪组织重塑的不利影响，这表明针对这些细胞中能量代谢的治疗潜力。控制 PDGFRβ+ 亚群谱系定型程度的因素尚不清楚。在这里，乔芬等人。证明线粒体活性决定脂肪细胞前体的细胞身份和谱系定向，并确定 PdgfRβ+ 细胞作为热量过量期间炎症和脂肪组织重塑的关键调节因子。
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 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. Factors controlling the degree of lineage commitment of PDGFRβ+ subpopulations are poorly defined. Here, Joffin et al. demonstrate that mitochondrial activity determines the cellular identity of adipocyte precursors and lineage commitment and pinpoint PdgfRβ+ cells as key regulators of inflammation and adipose tissue remodeling during caloric excess.
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影响因子：
20.3
作者：
Doughty, Cheryl A.;Bleiman, Blair F.;Chiles, Thomas C.
通讯作者：
Chiles, Thomas C.
影响因子：
4.4
作者：
Rodriguez-Prados, Juan-Carlos;Traves, Paqui G.;Bosca, Lisardo
通讯作者：
Bosca, Lisardo
影响因子：
7.7
作者：
Kusminski CM;Chen S;Ye R;Sun K;Wang QA;Spurgin SB;Sanders PE;Brozinick JT;Geldenhuys WJ;Li WH;Unger RH;Scherer PE
通讯作者：
Scherer PE
DOI：
10.1084/jem.20110278
发表时间：
2011-07-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shi LZ;Wang R;Huang G;Vogel P;Neale G;Green DR;Chi H
通讯作者：
Chi H
DOI：
10.4049/jimmunol.1003613
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Michalek RD;Gerriets VA;Jacobs SR;Macintyre AN;MacIver NJ;Mason EF;Sullivan SA;Nichols AG;Rathmell JC
通讯作者：
Rathmell JC