title: Role of PPAR gamma in regulating adipocyte differentiation and insulin-responsive glucose uptake.
abstract: 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 PPAR gamma 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/EBP beta, C/EBP delta, and glucocorticoids. Ectopic expression of PPAR gamma in non-adipogenic, Swiss 3T3 fibroblasts promotes their conversion into adipocytes as indicated by the accumulation of lipid droplets and the induction of C/EBP alpha, aP2, insulin-responsive aminopeptidase (IRAP), and glucose transporter 4 (GLUT4) expression. These PPAR gamma-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, PPAR gamma-expressing NIH-3T3 fibroblasts, despite similar lipid accumulation, adipocyte morphology, and aP2 expression, do not synthesize C/EBP alpha and fail to acquire insulin sensitivity. In Swiss 3T3 cells ectopically expressing PPAR gamma, the development of insulin-responsive glucose uptake correlates with C/EBP alpha expression. Furthermore, ectopic expression of C/EBP alpha in NIH-3T3 cells induces PPAR gamma expression and adipogenesis, but also restores insulin-sensitive glucose transport. These results suggest that although PPAR gamma is sufficient to trigger the adipogenic program, C/EBP alpha is required for establishment of insulin-sensitive glucose transport in adipocytes.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Hamm
authors.forename: A K
authors.initials: AK
authors.lastname: el Jack
authors.forename: P F
authors.initials: PF
authors.lastname: Pilch
authors.forename: S R
authors.initials: SR
authors.lastname: Farmer
mesh_terms: D016475:3T3 Cells / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D000077288:Troglitazone
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D002839:Chromans; D004268:DNA-Binding Proteins; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012795:Sialoglycoproteins; C495693:Slc2a4 protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone; D005947:Glucose