在脂肪细胞重塑过程中，脂滴结构通过肌动蛋白纤维的重组调节胰岛素敏感性。
During Adipocyte Remodeling, Lipid Droplet Configurations Regulate Insulin Sensitivity through F-Actin and G-Actin Reorganization.
机构信息
National Creative Research Initiatives Center for Adipose Tissue Remodeling, Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, South Korea.
Bioinformatics Institute, Seoul National University, Seoul, South Korea.
出版信息
Mol Cell Biol. 2019 Sep 27;39(20). doi: 10.1128/MCB.00210-19. Print 2019 Oct 15.
Adipocytes have unique morphological traits in insulin sensitivity control. However, how the appearance of adipocytes can determine insulin sensitivity has not been understood. Here, we demonstrate that actin cytoskeleton reorganization upon lipid droplet (LD) configurations in adipocytes plays important roles in insulin-dependent glucose uptake by regulating GLUT4 trafficking. Compared to white adipocytes, brown/beige adipocytes with multilocular LDs exhibited well-developed filamentous actin (F-actin) structure and potentiated GLUT4 translocation to the plasma membrane in the presence of insulin. In contrast, LD enlargement and unilocularization in adipocytes downregulated cortical F-actin formation, eventually leading to decreased F-actin-to-globular actin (G-actin) ratio and suppression of insulin-dependent GLUT4 trafficking. Pharmacological inhibition of actin polymerization accompanied with impaired F/G-actin dynamics reduced glucose uptake in adipose tissue and conferred systemic insulin resistance in mice. Thus, our study reveals that adipocyte remodeling with different LD configurations could be an important factor to determine insulin sensitivity by modulating F/G-actin dynamics.
脂肪细胞在胰岛素敏感性控制方面具有独特的形态特征。然而，脂肪细胞的外观如何决定胰岛素敏感性还没有被理解。在这里，我们证明了脂肪细胞中脂滴（LD）构型引起的肌动蛋白细胞骨架重排，通过调节 GLUT4 易位在胰岛素依赖性葡萄糖摄取中发挥重要作用。与白色脂肪细胞相比，具有多房 LD 的棕色/米色脂肪细胞表现出发达的丝状肌动蛋白（F-actin）结构，并在胰岛素存在的情况下增强 GLUT4 向质膜的易位。相比之下，脂肪细胞中 LD 的增大和单房化会下调皮质 F-actin 的形成，最终导致 F-actin 与球状肌动蛋白（G-actin）的比例降低，并抑制胰岛素依赖性 GLUT4 易位。肌动蛋白聚合的药理学抑制伴随着 F/G-actin 动力学的受损，减少了脂肪组织中的葡萄糖摄取，并导致小鼠全身胰岛素抵抗。因此，我们的研究表明，具有不同 LD 构型的脂肪细胞重塑可能是通过调节 F/G-actin 动力学来决定胰岛素敏感性的一个重要因素。
Zotero 插件