Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia

Dev Cell. 2002 Mar;2(3):331-41. doi: 10.1016/s1534-5807(02)00131-4.


Cellular differentiation involves transcriptional responses to environmental stimuli. Adipocyte differentiation is inhibited under hypoxic conditions, indicating that oxygen (O(2)) is an important physiological regulator of adipogenesis. Hypoxia inhibits PPAR gamma 2 nuclear hormone receptor transcription, and overexpression of PPAR gamma 2 or C/EBP beta stimulates adipogenesis under hypoxia. Mouse embryonic fibroblasts deficient in hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) are refractory to hypoxia-mediated inhibition of adipogenesis. The HIF-1-regulated gene DEC1/Stra13, a member of the Drosophila hairy/Enhancer of split transcription repressor family, represses PPAR gamma 2 promoter activation and functions as an effector of hypoxia-mediated inhibition of adipogenesis. These data indicate that an O(2)-sensitive signaling mechanism regulates adipogenesis. Thus, agents that regulate HIF-1 activity or O(2) sensing may be used to inhibit adipogenesis and control obesity.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / physiology*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation / physiology
  • Cell Hypoxia / physiology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Homeodomain Proteins / genetics*
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mice
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Oxygen / pharmacology
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Transcription Factors / genetics*


  • Basic Helix-Loop-Helix Transcription Factors
  • Bhlhe40 protein, mouse
  • DNA-Binding Proteins
  • Hif1a protein, mouse
  • Homeodomain Proteins
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Oxygen