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标题：Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation
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作者：Fu, Yuchang ; Luo, Nanlan ; Klein, Richard L. 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2005
卷号：46
期号：07
页码：1369-1379
DOI：10.1194/jlr.M400373-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Adiponectin is secreted from adipocytes, and low circulatinglevels have been epidemiologically associated with obesity,insulin resistance, type 2 diabetes, and cardiovascular disease.To investigate whether adiponectin could exert autocrine effectsin adipocytes, we expressed the adiponectin gene in 3T3-L1 fibroblasts.We observed that 3T3-L1 fibroblasts expressing adiponectin havea fast growth phase and reach confluence more rapidly comparedwith control cells or LacZ-transduced cells. Furthermore, cellswith overexpressed adiponectin were observed to differentiateinto adipocytes more rapidly, and during adipogenesis, theyexhibited more prolonged and robust gene expression for relatedtranscriptional factors, CCAAT/enhancer binding protein ${alpha}$ (C/EBP2),peroxisome proliferator-activated receptor ${gamma}$ (PPAR ${gamma}$ ), and adipocytedetermination and differentiation factor 1/sterol-regulatoryelement binding protein 1c (ADD1/SREBP1c) and earlier suppressionof PPAR ${gamma}$ coactivator-1 ${alpha}$ (PGC-1 ${alpha}$ ). In fully differentiated adipocytes,adiponectin-overexpressing cells accumulated more and largerlipid droplets compared with control cells. Also, adiponectinincreased insulin's ability to maximally stimulate glucose uptakeby 78% through increased glucose transporter 4 (GLUT4) geneexpression and increased GLUT4 recruitment to the plasma membrane. These data suggest a new role for adiponectin as an autocrinefactor in adipose tissues: promoting cell proliferation anddifferentiation from preadipocytes into adipocytes, augmentingprogrammed gene expression responsible for adipogenesis, andincreasing lipid content and insulin responsiveness of the glucosetransport system in adipocytes. Supplementary key words obesity/diabetes • gene expression • adipocytokine • glucose • lipid metabolism