Submitted on September 28, 2004
Revised on March 28, 2005
Accepted on April 3, 2005
Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation: potential role in autoregulation of adipocyte metabolism and adipose mass
Yuchang Fu, Nanlan Luo, Richard L. Klein, and W. Timothy Garvey
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360
Corresponding Author: yfu{at}uab.edu
Adiponectin (Ad) 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 using a lentiviral vector, and selected several stably-transduced cell lines under blasticidin selection. We observed that 3T3-L1 fibroblast cell lines expressing adiponectin have a fast growth phase and reach confluence more rapidly when compared with control cells or LacZ transduced cell lines. Furthermore, cells with overexpressed adiponectin were observed to differentiate into adipocytes more rapidly, and, during adipogenesis, exhibited more prolonged and robust gene expression for related transcriptional factors (CCAAT/enhancer binding protein C/EBPperoxisome proliferator-activated receptor gamma (PPAR), and ADD1/SREBP1c, and earlier suppression of PGC-1. In fully differentiated adipocytes, both low and high adiponectin overexpressing cell lines accumulated more and larger lipid droplets when compared with control cells. Also, adiponectin increased insulin’s ability to maximally stimulate glucose uptake by 78 % through elevated glucose transporter GLUT4 gene expression and increased GLUT4 recruitment to the plasma membrane. In conclusion, adiponectin overexpression in stably transduced 3T3-L1 cells resulted in: 1) A more rapid cell proliferation in fibroblasts, and more rapid differentiation from preadipocytes into adipocytes; 2) Augmentation of programmed gene expression responsible for adipogenesis; 3) Increased lipid content and insulin responsiveness of the glucose transport system in fully differentiated adipocytes.
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