Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
Global Computational Biology and Digital Sciences, Boehringer Ingelheim Pharma GmbH and Co. KG, Biberach/Riss, Biberach, Germany.
Nat Metab. 2022 Jan;4(1):90-105. doi: 10.1038/s42255-021-00509-1. Epub 2022 Jan 13.
Healthy adipose tissue remodeling depends on the balance between de novo adipogenesis from adipogenic progenitor cells and the hypertrophy of adipocytes. De novo adipogenesis has been shown to promote healthy adipose tissue expansion, which confers protection from obesity-associated insulin resistance. Here, we define the role and trajectory of different adipogenic precursor subpopulations and further delineate the mechanism and cellular trajectory of adipogenesis, using single-cell RNA-sequencing datasets of murine adipogenic precursors. We identify Rspo2 as a functional regulator of adipogenesis, which is secreted by a subset of CD142 cells to inhibit maturation of early progenitors through the receptor Lgr4. Increased circulating RSPO2 in mice leads to adipose tissue hypertrophy and insulin resistance and increased RSPO2 levels in male obese individuals correlate with impaired glucose homeostasis. Taken together, these findings identify a complex cellular crosstalk that inhibits adipogenesis and impairs adipose tissue homeostasis.
健康的脂肪组织重塑取决于从脂肪生成祖细胞中新生脂肪生成与脂肪细胞肥大之间的平衡。新生脂肪生成已被证明可促进健康的脂肪组织扩张，从而防止与肥胖相关的胰岛素抵抗。在这里，我们使用小鼠脂肪生成前体细胞的单细胞 RNA 测序数据集，定义了不同脂肪生成前体亚群的作用和轨迹，并进一步阐述了脂肪生成的机制和细胞轨迹。我们确定 Rspo2 是脂肪生成的功能调节剂，它由一组 CD142 细胞分泌，通过受体 Lgr4 抑制早期祖细胞的成熟。在小鼠中循环 RSPO2 的增加导致脂肪组织肥大和胰岛素抵抗，而肥胖男性中 RSPO2 水平的增加与葡萄糖稳态受损相关。总之，这些发现确定了一种抑制脂肪生成和破坏脂肪组织动态平衡的复杂细胞串扰。
