Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation.
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 (PPARgamma), and adipocyte determination and differentiation factor 1/sterol-regulatory element binding protein 1c (ADD1/SREBP1c) and earlier suppression of PPARgamma coactivator-1alpha (PGC-1alpha). 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
Yuchang
Y
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294-3360, USA. yfu@uab.edu
Luo
Nanlan
N
Klein
Richard L
RL
Garvey
W Timothy
WT
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D052242:Adiponectin; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000096:biosynthesis; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000502:physiology*; D050356:Lipid Metabolism; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009124:Muscle Proteins / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis
D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C495693:Slc2a4 protein, mouse; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors