Role of PPAR gamma in regulating adipocyte differentiation and insulin-responsive glucose uptake

Ann N Y Acad Sci. 1999 Nov 18;892:134-45. doi: 10.1111/j.1749-6632.1999.tb07792.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • CCAAT-Enhancer-Binding Proteins
  • Chromans
  • DNA-Binding Proteins
  • Glucose Transporter Type 1
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Sialoglycoproteins
  • Slc2a4 protein, mouse
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Troglitazone
  • Glucose