The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II is a critical regulator of adipogenesis

Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2421-6. doi: 10.1073/pnas.0707082105. Epub 2008 Feb 4.

Abstract

The orphan nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII; Nr2f2) is expressed in adipose tissue in vivo and declines during differentiation. Overexpression of COUP-TFII prevents adipogenesis, whereas shRNA-mediated reduction of COUP-TFII promotes differentiation, as shown by increased lipid accumulation and elevated expression of fat cell marker proteins. Furthermore, reduction of COUP-TFII allows uncommitted fibroblasts to be differentiated into fat cells. COUP-TFII represses the expression of a number of proadipogenic factors in adipocytes, with direct action noted at the CAAT enhancer-binding protein alpha promoter. We show that COUP-TFII acts downstream of hedgehog signaling and is required for the full antiadipogenic effect of this pathway. This effect is mediated in part by interaction with GATA factors. COUP-TFII and GATA2 are physically associated and repress target gene expression in an additive manner. Taken together, our data demonstrate that COUP-TFII represents an endogenous suppressor of adipogenesis, linking antiadipogenic extracellular signals to the core transcriptional cascade.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipogenesis*
  • Adipose Tissue / metabolism
  • Animals
  • COUP Transcription Factor II / genetics*
  • COUP Transcription Factor II / metabolism*
  • Chickens
  • GATA Transcription Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins / metabolism
  • Mice
  • Ovalbumin / metabolism*
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • COUP Transcription Factor II
  • GATA Transcription Factors
  • Hedgehog Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Ovalbumin