Role of PPARγ in Regulating Adipocyte Differentiation and Insulin-Responsive Glucose Uptake

• Published in: Annals of the New York Academy of Sciences 1999-11, Vol.892 (1), p.134-145
• Main Authors: HAMM, JONATHAN K., EL JACK, AMR K., PILCH, PAUL F., FARMER, STEPHEN R.
• Format: Article
• Language: English
• Subjects: 3T3 Cells - metabolism; Adipocytes - metabolism; Animals; CCAAT-Enhancer-Binding Proteins; Chromans - pharmacology; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation - drug effects; Glucose - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 4; Hypoglycemic Agents - pharmacology; Interleukin 1 Receptor Antagonist Protein; Mice; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Sialoglycoproteins - metabolism; Thiazoles - pharmacology; Thiazolidinediones; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic - drug effects; Troglitazone
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.1999.tb07792.x

Adipocyte differentiation is regulated by at least two families of transcription factors, CCAAT/enhancer binding proteins (C/EBPs) and peroxisome proliferator‐activated receptors (PPARs). Induction of PPARγ gene transcription during the differentiation of preadipocytes into adipocytes in vitro occurs following an initial phase of cell proliferation and requires a direct involvement of C/EBPβ, C/EBPδ, and glucocorticoids. Ectopic expression of PPARγ in non‐adipogenic, Swiss 3T3 fibroblasts promotes their conversion into adipocytes as indicated by the accumulation of lipid droplets and the induction of C/EBPα, aP2, insulin‐responsive aminopeptidase (IRAP), and glucose transporter 4 (GLUT4) expression. These PPARγ‐expressing Swiss cells also exhibit a high level of insulin‐responsive glucose uptake that is comparable to that expressed in 3T3‐L1 adipocytes. In contrast, PPARγ‐expressing NIH‐3T3 fibroblasts, despite similar lipid accumulation, adipocyte morphology, and aP2 expression, do not synthesize C/EBPα and fail to acquire insulin sensitivity. In Swiss 3T3 cells ectopically expressing PPARγ, the development of insulin‐responsive glucose uptake correlates with C/EBPα expression. Furthermore, ectopic expression of C/EBPα in NIH‐3T3 cells induces PPARγ expression and adipogenesis, but also restores insulin‐sensitive glucose transport. These results suggest that although PPARγ is sufficient to trigger the adipogenic program, C/EBPα is required for establishment of insulin‐sensitive glucose transport in adipocytes.