snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis

snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis
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DOI:
10.1038/s41586-020-2856-x
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发表时间:
2020-10-28
期刊:
影响因子:
64.8
通讯作者:
Wolfrum, Christian
Wolfrum, Christian
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Sun, Wenfei;Dong, Hua;Wolfrum, Christian

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脂肪组织通常根据其功能分为白色、棕色或米色(brite)(1)。它是全身代谢的重要调节剂,如肥胖症中脂肪组织功能障碍导致各种继发性代谢并发症的事实所示(2,3)。此外,脂肪组织作为信号中枢,通过旁分泌和内分泌信号调节全身代谢(4)。在这里,我们使用小鼠和人类的单核RNA测序(snRNA-seq)分析来表征脂肪细胞的异质性。我们确定了一种罕见的小鼠脂肪细胞亚群,在较高的温度下增加丰度,我们表明,这个亚群通过醋酸盐介导的调节其产热能力调节邻近脂肪细胞的活性。人脂肪组织含有更多数量的该亚群细胞,这可以解释与小鼠脂肪组织相比人的产热活性较低,并表明靶向该途径可用于恢复产热活性。
Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite)(1). It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications(2,3). In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals(4). Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity.