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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

1
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.

Abstract

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.

PMID:
18187772
DOI:
10.1194/jlr.M700545-JLR200
[Indexed for MEDLINE]
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