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 (C/EBP2),peroxisome proliferator-activated receptor (PPAR), and adipocytedetermination and differentiation factor 1/sterol-regulatoryelement binding protein 1c (ADD1/SREBP1c) and earlier suppressionof PPAR coactivator-1 (PGC-1). 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