Berberine exerts anti-adipogenic activity through up-regulation of C/EBP inhibitors, CHOP and DEC2

Biochem Biophys Res Commun. 2011 Sep 23;413(2):376-82. doi: 10.1016/j.bbrc.2011.08.110. Epub 2011 Aug 27.

Abstract

Berberine exerts an anti-adipogenic activity that is associated with the down-regulation of C/EBPα and PPARγ. Stimulation of AMP-activated kinase (AMPK) caused by inhibition of mitochondrial respiration has been suggested to underlie such molecular regulation. In the present study, we show that berberine up-regulated the expression of two different sets of C/EBP inhibitors, CHOP and DEC2, while down-modulating C/EBPα, PPARγ and other adipogenic markers and effectors in differentiating 3T3-L1 preadipocytes and mature adipocytes. Data also suggested that the berberine-induced up-regulation of CHOP and DEC2 was attributable to selective activation of an unfolded protein response (UPR) and modified extracellular environment, respectively. As a result, the anti-adipogenic activity of berberine was diminished remarkably by adjusting the differentiation culture media and limitedly but consistently by knockdown of CHOP expression. Together, up-regulation of C/EBP inhibitors appears to underlie the berberine-induced repression of C/EBPα and PPARγ and, so, the inhibition of adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Berberine / pharmacology*
  • CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors*
  • Male
  • Mice
  • Transcription Factor CHOP / biosynthesis*
  • Transcription Factors / biosynthesis*
  • Up-Regulation

Substances

  • Bhlhb3 protein, mouse
  • CCAAT-Enhancer-Binding Proteins
  • Ddit3 protein, mouse
  • Transcription Factors
  • Berberine
  • Transcription Factor CHOP