Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation
Glycogen Dynamics Drives Lipid Droplet Biogenesis during Brown Adipocyte Differentiation
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DOI：
10.1016/j.celrep.2019.09.073
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发表时间：
2019-11-05
期刊：
影响因子：
8.8
通讯作者：
Duez, Helene
中科院分区：
文献类型：
--
作者：
Mayeuf-Louchart, Alicia;Lancel, Steve;Duez, Helene
来源于祖细胞或诱导多能干细胞（iPSC）的棕色脂肪组织（BAT）或棕色/米色脂肪细胞的布朗宁诱导或移植可以代表治疗代谢疾病的有力策略。然而，我们对棕色脂肪细胞的分化和活化机制的理解不足限制了这种治疗的发展。尽管大多数研究都是使用体外培养的前脂肪细胞进行的，但已经确定了控制棕色脂肪细胞分化的各种遗传因素。我们在此研究小鼠胚胎脂肪祖细胞向棕色脂肪细胞的分化。我们证明了多个脂滴（LD）的形成是在糖原簇内开始的，糖原簇通过糖噬作用降解，以提供从头脂肪生成和LD形成所必需的代谢底物。因此，本研究揭示了糖原在LD产生中的作用。
Browning induction or transplantation of brown adipose tissue (BAT) or brown/beige adipocytes derived from progenitor or induced pluripotent stem cells (iPSCs) can represent a powerful strategy to treat metabolic diseases. However, our poor understanding of the mechanisms that govern the differentiation and activation of brown adipocytes limits the development of such therapy. Various genetic factors controlling the differentiation of brown adipocytes have been identified, although most studies have been performed using in vitro cultured pre-adipocytes. We investigate here the differentiation of brown adipocytes from adipose progenitors in the mouse embryo. We demonstrate that the formation of multiple lipid droplets (LDs) is initiated within clusters of glycogen, which is degraded through glycophagy to provide the metabolic substrates essential for de novo lipogenesis and LD formation. Therefore, this study uncovers the role of glycogen in the generation of LDs.