Audano Matteo, Pedretti Silvia, Ligorio Simona, Gualdrini Francesco, Polletti Sara, Russo Marta, Ghisletti Serena, Bean Camilla, Crestani Maurizio, Caruso Donatella, De Fabiani Emma, Mitro Nico
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
J Cell Biol. 2021 Mar 1;220(3). doi: 10.1083/jcb.202003173.
The commitment of mesenchymal stem cells to preadipocytes is stimulated by hormonal induction. Preadipocytes induced to differentiate repress protein synthesis, remodel their cytoskeleton, and increase mitochondrial function to support anabolic pathways. These changes enable differentiation into mature adipocytes. Our understanding of the factors that coordinately regulate the early events of adipocyte differentiation remains incomplete. Here, by using multipronged approaches, we have identified zinc finger CCCH-type containing 10 (Zc3h10) as a critical regulator of the early stages of adipogenesis. Zc3h10 depletion in preadipocytes resulted in increased protein translation and impaired filamentous (F)-actin remodeling, with the latter detrimental effect leading to mitochondrial and metabolic dysfunction. These defects negatively affected differentiation to mature adipocytes. In contrast, Zc3h10 overexpression yielded mature adipocytes with remarkably increased lipid droplet size. Overall, our study establishes Zc3h10 as a fundamental proadipogenic transcription factor that represses protein synthesis and promotes F-actin/mitochondria dynamics to ensure proper energy metabolism and favor lipid accumulation.
间充质干细胞向脂肪前体细胞的定向分化受激素诱导刺激。诱导分化的脂肪前体细胞会抑制蛋白质合成、重塑其细胞骨架并增强线粒体功能以支持合成代谢途径。这些变化促使其分化为成熟脂肪细胞。我们对协同调节脂肪细胞分化早期事件的因素的理解仍不完整。在此，通过多种方法，我们确定含锌指CCCH型结构域10（Zc3h10）是脂肪生成早期阶段的关键调节因子。脂肪前体细胞中Zc3h10的缺失导致蛋白质翻译增加和丝状（F）-肌动蛋白重塑受损，后一种有害作用导致线粒体和代谢功能障碍。这些缺陷对向成熟脂肪细胞的分化产生负面影响。相反，Zc3h10的过表达产生了脂滴大小显著增加的成熟脂肪细胞。总体而言，我们的研究确定Zc3h10是一种基本的促脂肪生成转录因子，它抑制蛋白质合成并促进F-肌动蛋白/线粒体动态变化，以确保适当的能量代谢并有利于脂质积累。
