Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis
Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis
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DOI：
10.1016/j.celrep.2021.108817
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发表时间：
2021-03-09
期刊：
影响因子：
8.8
通讯作者：
Inagaki, Masaki
中科院分区：
文献类型：
--
作者：
Yamakawa, Daishi;Katoh, Daisuke;Inagaki, Masaki
初级纤毛在信号转导和发育中起着关键作用，并且已知作为信号中枢。最近的研究表明，原发性纤毛功能障碍影响脂肪形成，但其机制尚不清楚。在这里，我们表明，缺乏毛蛋白（纤毛形成的关键调节因子）的间充质祖细胞C3 H10 T1/2具有比对照细胞显着更长的纤毛，并且无法分化为脂肪细胞。在机制上，伸长的纤毛防止小窝蛋白-1-和/或GM 3-阳性脂筏在胰岛素受体蛋白聚集的纤毛基部周围组装，从而抑制胰岛素Akt信号传导。我们进一步产生了脂蛋白基因敲除小鼠，其中成脂祖细胞显示细长的纤毛并损害脂筏动力学。与野生型（WT）小鼠相比，长期高脂饮食的基因敲除小鼠表现出减少的体脂和更小的脂肪细胞。总的来说，我们的研究结果表明，初级纤毛在调节成脂信号转导通过控制周围的纤毛脂筏动力学的作用。
Primary cilia play a pivotal role in signal transduction and development and are known to serve as signaling hubs. Recent studies have shown that primary cilium dysfunction influences adipogenesis, but the mechanisms are unclear. Here, we show that mesenchymal progenitors C3H10T1/2 depleted of trichoplein, a key regulator of cilium formation, have significantly longer cilia than control cells and fail to differentiate into adipocytes. Mechanistically, the elongated cilia prevent caveolin-1- and/or GM3-positive lipid rafts from being assembled around the ciliary base where insulin receptor proteins accumulate, thereby inhibiting the insulinAkt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockoutmice on an extended high-fat diet exhibit reduced body fat and smaller adipocytes than wild-type (WT) mice. Overall, our results suggest a role for primary cilia in regulating adipogenic signal transduction via control of the lipid raft dynamics around cilia.