O-GlcNAc modification of PPARγ reduces its transcriptional activity

Biochem Biophys Res Commun. 2012 Jan 27;417(4):1158-63. doi: 10.1016/j.bbrc.2011.12.086. Epub 2011 Dec 27.


The peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The β-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPARγ is modified by O-GlcNAc in 3T3-L1 adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPARγ is the major O-GlcNAc site. Transcriptional activity of wild type PPARγ was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPARγ did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPARγ transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPARγ influences its transcriptional activity and is involved in adipocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / antagonists & inhibitors
  • Acetylglucosamine / metabolism*
  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects
  • Adipogenesis / genetics*
  • Animals
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • HeLa Cells
  • Humans
  • Mice
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Protein Processing, Post-Translational*
  • Transcription, Genetic*


  • 1,2-dideoxy-2'-propylglucopyranoso(2,1-d)-delta 2'-thiazoline
  • Bridged Bicyclo Compounds, Heterocyclic
  • PPAR gamma
  • Acetylglucosamine