Hypoxia inhibits adipocyte differentiation in a HDAC-independent manner

Ho Kim Kang, Jeong Song Min, Jieun Chung, Hyunsung Park, Bum Kim Jae

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Oxygen is the most important factor for the appropriate regulation of multiple energy homeostasis and cell differentiation. Although hypoxia-induced signaling cascades have been intensively studied, the molecular mechanism by which hypoxic signals suppress adipocyte differentiation is unclear. Here, we demonstrated that repression of adipocyte differentiation by hypoxia and HIF1α- or Stra13-overexpression was not associated with HDACs. Furthermore, HDACs did not affect inhibitory effect of Stra13 on PPARγ promoter activity, although the hypoxia-induced suppression of adipogenesis was accompanied with reduced acetylation of histone H3 and H4 at the PPARγ promoter. Instead, we revealed that hypoxic circumstances biphasically activated AMPK and concomitantly blocked clonal expansion of preadipocytes, which is an indispensable step for early phase of adipocyte differentiation. Taken together, these results suggest that hypoxic condition attenuates adipocyte differentiation by inhibition of PPARγ expression in a HDAC-independent manner and by activation of AMPK which impairs clonal expansion phase.

Original languageEnglish
Pages (from-to)1178-1184
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume333
Issue number4
DOIs
StatePublished - 12 Aug 2005

Keywords

  • Adipocyte differentiation
  • Clonal expansion
  • HDAC
  • Hypoxia
  • Stra13

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