Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation
Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation
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DOI：
10.1194/jlr.m400373-jlr200
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发表时间：
2005-07-01
影响因子：
6.5
通讯作者：
Garvey, WT
中科院分区：
文献类型：
--
作者：
Fu, YC;Luo, NL;Garvey, WT
脂联素由脂肪细胞分泌，在流行病学上，其循环水平低与肥胖、胰岛素抵抗、2型糖尿病和心血管疾病相关。为了研究脂联素是否能在脂肪细胞中发挥自分泌作用，我们在3T3 - L1成纤维细胞中表达脂联素基因。我们观察到，与对照细胞或LacZ转导细胞相比，表达脂联素的3T3 - L1成纤维细胞具有快速生长期，并且更快地达到汇合。此外，观察到脂联素过表达的细胞更快地分化为脂肪细胞，并且在脂肪生成过程中，它们对于相关转录因子，如CCAAT/增强子结合蛋白α（C/EBP2）、过氧化物酶体增殖物激活受体γ（PPARγ）以及脂肪细胞决定和分化因子1/固醇调节元件结合蛋白1c（ADD1/SREBP1c）表现出更持久和更强的基因表达，并且更早地抑制PPARγ共激活因子 - 1α（PGC - 1α）。在完全分化的脂肪细胞中，与对照细胞相比，脂联素过表达的细胞积累了更多且更大的脂滴。此外，脂联素通过增加葡萄糖转运蛋白4（GLUT4）的基因表达以及增加GLUT4向质膜的募集，使胰岛素最大程度刺激葡萄糖摄取的能力提高了78%。这些数据表明脂联素作为一种自分泌因子在脂肪组织中具有新的作用：促进细胞增殖以及从前脂肪细胞向脂肪细胞的分化，增强负责脂肪生成的程序性基因表达，并增加脂肪细胞中脂质含量以及葡萄糖转运系统的胰岛素敏感性。——傅（Fu），Y.，N. 罗（Luo），R. L. 克莱因（Klein），W. T. 加维（Garvey）。脂联素促进脂肪细胞分化、胰岛素敏感性和脂质积累。
Adiponectin is secreted from adipocytes, and low circulating levels have been epidemiologically associated with obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. To investigate whether adiponectin could exert autocrine effects in adipocytes, we expressed the adiponectin gene in 3T3-L1 fibroblasts. We observed that 3T3-L1 fibroblasts expressing adiponectin have a fast growth phase and reach confluence more rapidly compared with control cells or LacZ-transduced cells. Furthermore, cells with overexpressed adiponectin were observed to differentiate into adipocytes more rapidly, and during adipogenesis, they exhibited more prolonged and robust gene expression for related transcriptional factors, CCAAT/enhancer binding protein alpha (C/EBP2), peroxisome proliferator-activated receptor gamma ( PPAR gamma), and adipocyte determination and differentiation factor 1/stero/regulatory element binding protein 1c ( ADD1/SREBP1c) and earlier suppression of PPAR gamma coactivator-1 alpha (PGC-1 alpha). In fully differentiated adipocytes, adiponectin-overexpressing cells accumulated more and larger lipid droplets compared with control cells. Also, adiponectin increased insulin's ability to maximally stimulate glucose uptake by 78% through increased glucose transporter 4 ( GLUT4) gene expression and increased GLUT4 recruitment to the plasma membrane. These data suggest a new role for adiponectin as an autocrine factor in adipose tissues: promoting cell proliferation and differentiation from preadipocytes into adipocytes, augmenting programmed gene expression responsible for adipogenesis, and increasing lipid content and insulin responsiveness of the glucose transport system in adipocytes. - Fu, Y., N. Luo, R. L. Klein, and W. T. Garvey. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation.