Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice.
Pdgfrβ+ Mural Preadipocytes Contribute to Adipocyte Hyperplasia Induced by High-Fat-Diet Feeding and Prolonged Cold Exposure in Adult Mice.
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DOI：
10.1016/j.cmet.2015.10.018
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发表时间：
2016-02-09
期刊：
影响因子：
29
通讯作者：
Gupta RK
中科院分区：
文献类型：
--
作者：
Vishvanath L;MacPherson KA;Hepler C;Wang QA;Shao M;Spurgin SB;Wang MY;Kusminski CM;Morley TS;Gupta RK
肥胖时白色脂肪组织(WAT)的扩张涉及新生脂肪细胞的从头分化；然而，这些细胞的细胞来源尚不清楚。在这里，我们利用Zfp423GFP报告鼠来表征具有不同水平的前脂肪细胞承诺因子Zfp423的脂肪壁细胞(PDGFRβ+)。我们发现脂肪组织包含不同的壁细胞群，Zfp423的水平区分成脂细胞和炎性壁细胞。使用我们的“MuralChaser”血统追踪系统，我们发现血管周围脂肪细胞是肥胖形成的脂肪细胞的发育前体，脂肪生成和前体丰度以依赖于仓库的方式调节。有趣的是，PDGFRβ+细胞在最初冷诱导的WAT中对米色脂肪细胞的募集没有显著贡献；只有在长期冷暴露后，这些细胞才分化为米色脂肪细胞。这些结果为肥胖症中白色脂肪细胞的壁细胞起源提供了遗传学证据，并表明米色脂肪形成可能来自多种来源。
The expansion of white adipose tissue (WAT) in obesity involves de novo differentiation of new adipocytes; however, the cellular origin of these cells remains unclear. Here, we utilize Zfp423GFP reporter mice to characterize adipose mural (Pdgfrβ+) cells with varying levels of the preadipocyte commitment factor Zfp423. We find that adipose tissue contains distinct mural populations, with levels of Zfp423 distinguishing adipogenic from inflammatory-like mural cells. Using our “MuralChaser” lineage tracking system, we uncover adipose perivascular cells as developmental precursors of adipocytes formed in obesity, with adipogenesis and precursor abundance regulated in a depot-dependent manner. Interestingly, Pdgfrβ+ cells do not significantly contribute to the initial cold-induced recruitment of beige adipocytes in WAT; it is only after prolonged cold exposure that these cells differentiate into beige adipocytes. These results provide genetic evidence for a mural cell origin of white adipocytes in obesity, and suggest that beige adipogenesis may originate from multiple sources.