TRB3 suppresses adipocyte differentiation by negatively regulating PPARgamma transcriptional activity

J Lipid Res. 2008 Apr;49(4):880-92. doi: 10.1194/jlr.M700545-JLR200. Epub 2008 Jan 10.


In the course of an effort to identify the regulators for peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent perilipin gene expression, we found that tribbles homolog 3 (TRB3), containing a single kinase domain without enzymatic activity, downregulates PPARgamma transcriptional activities by protein-protein interaction. We examined the role that TRB3 plays in adipocyte differentiation in 3T3-L1 cells. TRB3 gene and protein expression was increased during adipocyte differentiation concomitantly with an increase in the mRNA levels of CCAAT/enhancer binding protein homologous protein. The physical interaction between TRB3 and PPARgamma was also verified in 3T3-L1 adipocytes. Forced TRB3 expression in 3T3-L1 cells decreased the mRNA levels of PPARgamma-target genes and intracellular triglyceride levels, whereas knockdown of TRB3 expression by RNA interference increased them. TRB3 also inhibits PPARgamma-dependent adipocyte differentiation in lentivirus-mediated PPARgamma-expressing 3T3-L1 cells. These results provide evidence that TRB3 acts as a potent negative regulator of PPARgamma, a master regulator of adipocyte differentiation, and tightly controls adipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism*
  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Humans
  • Mice
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic / genetics*


  • Cell Cycle Proteins
  • PPAR gamma
  • RNA, Messenger
  • Repressor Proteins
  • TRB3 protein, mouse
  • TRIB3 protein, human
  • Protein Serine-Threonine Kinases