Department of Cell and Molecular Biology, Tulane University, New Orleans, United States.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Disease, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Elife. 2022 May 3;11:e77740. doi: 10.7554/eLife.77740.
Wnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of adipocytes that exhibit persistent activity of Wnt/β-catenin signaling, as revealed by the Tcf/Lef-GFP reporter allele, in embryonic and adult mouse fat depots, named as Wnt adipocytes. We showed that this β-catenin-mediated signaling activation in these cells is Wnt ligand- and receptor-independent but relies on AKT/mTOR pathway and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes convert into beige adipocytes directly and are also required for beige fat recruitment under thermal challenge, demonstrating both cell autonomous and non-cell autonomous roles in adaptive thermogenesis. Furthermore, mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging in adipose tissues and systemic glucose homeostasis.
Wnt/β-catenin 信号通路已被证实是脂肪生成的有效抑制剂。在这里，我们鉴定了一群脂肪细胞，这些细胞在胚胎期和成年期的小鼠脂肪组织中表现出持续的 Wnt/β-catenin 信号活性，被命名为 Wnt 脂肪细胞。我们表明，这些细胞中 β-连环蛋白介导的信号激活是 Wnt 配体和受体非依赖性的，但依赖于 AKT/mTOR 途径，对于细胞存活是必需的。这些脂肪细胞在转录组和基因组特征上与经典脂肪细胞不同，可从各种间充质基质细胞来源包括人细胞中诱导产生。遗传谱系追踪和靶向细胞消融研究表明，这些脂肪细胞可直接转化为米色脂肪细胞，并且在热应激下招募米色脂肪细胞也是必需的，这表明它们在适应性产热中具有细胞自主和非细胞自主的作用。此外，携带这些脂肪细胞靶向消融的小鼠表现出葡萄糖不耐受，而接受外源性供应这些细胞的小鼠表现出增强的葡萄糖利用。我们的研究揭示了一个独特的脂肪细胞群体在调节脂肪组织中的米色化和全身葡萄糖稳态中的作用。
