TRB3 suppresses adipocyte differentiation by negatively regulating PPARgamma transcriptional activity.
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.
Takahashi
Yu
Y
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
Ohoka
Nobumichi
N
Hayashi
Hidetoshi
H
Sato
Ryuichiro
R
D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000037:antagonists & inhibitors; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*
D018797:Cell Cycle Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D012097:Repressor Proteins; C474830:TRB3 protein, mouse; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases