Send to

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

TRB3 suppresses adipocyte differentiation by negatively regulating PPARgamma transcriptional activity.

Author information

Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.


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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center