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Journal of Lipid Research, Vol. 46, 1369-1379, July 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology
Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation
* Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360
Department of Medicine, Medical University of South Carolina, and Charleston VA Medical Center, Charleston, SC 29425
Birmingham VA Medical Center, Birmingham, AL 35233
Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M400373-JLR200
1 To whom correspondence should be addressed. e-mail: yfu{at}uab.edu
in re-
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 
(C/EBP2), peroxisome proliferator-activated receptor 
(PPAR), and adipocyte determination and differentiation factor 1/sterol-regulatory element binding protein 1c (ADD1/SREBP1c) and earlier suppression of PPAR coactivator-1 (PGC-1). 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.
Supplementary key words obesity/diabetes • gene expression • adipocytokine • glucose • lipid metabolism
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