Cell
Volume 79, Issue 7, 30 December 1994, Pages 1147-1156
Journal home page for Cell

Article
Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factor

https://doi.org/10.1016/0092-8674(94)90006-XGet rights and content

Abstract

Peroxisome proliferator-activated receptor γ2 (PPARγ2) is an adipocyte-specific nuclear hormone receptor that has recently been identified as a key regulator of two fat cell enhancers. Transcriptional activation by PPARγ2 is potentiated by a variety of lipids and lipid-like compounds, including naturally occurring polyunsaturated fatty acids. We demonstrate here that retroviral expression of PPARγ2 stimulates adipose differentiation of cultured fibroblasts. PPAR activators promote the differentiation of PPARγ2-expressing cells in a dose-dependent manner. CEBPα, a second transcription factor induced during adipocyte differentiation, can cooperate with PPARγ2 to stimulate the adipocyte program dramatically. Our results suggest that the physiologic role of PPARγ2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism.

References (49)

  • G. Ailhaud et al.

    Cellular and molecular aspects of adipose tissue development

    Annu. Rev. Nutr.

    (1992)
  • P.H. Bennet

    Epidemiology of diabetes mellitus

  • A. Chawla et al.

    Peroxisome proliferator and retinoid signalling pathways co-regulate preadipocyte phenotype and survival

  • J.M. Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • R.J. Christy et al.

    Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes

    Genes Dev.

    (1989)
  • S. Enerback et al.

    Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cis-regulatory regions, LP-α and LP-β, of importance for the differentiation-linked induction of the LPL gene during adipogenesis

    Mol. Cell. Biol.

    (1992)
  • A.P. Fineberg et al.

    A technique for radiolabeling DNA restriction fragments to high specific activity

    Anal. Biochem.

    (1984)
  • S.O. Freytag et al.

    Reciprocal regulation of adipogenesis by Myc and CEBPα

    Science

    (1992)
  • S.O. Freytag et al.

    Ectopic expression of the CCAAT/enhancer-binding protein a promotes the adipogenic program in a variety of mouse fibroblastic cells

    Genes Dev.

    (1994)
  • A.D. Friedman et al.

    CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells

    Genes Dev.

    (1989)
  • V. Giguere et al.

    Isoform-specific amino terminal domains dictate DNA binding properties of ROR-α, a novel family of orphan hormone nuclear receptors

    Genes Dev.

    (1994)
  • M. Gottlicher et al.

    Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor

  • R.A. Graves et al.

    Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor

    Genes Dev.

    (1991)
  • R.A. Graves et al.

    Analysis of a tissue-specific enhancer: ARF6 regulates adipogenic gene expression

    Mol. Cell. Biol.

    (1992)
  • Cited by (3212)

    View all citing articles on Scopus
    View full text