BPB Reports

Paper Details

BPB Reports
Vol. 3 No. 4 p.119-125 2020
Regular Article
Thiazolidinediones Downregulate PPARγ Expression via Induction of aP2 During Mouse 3T3-L1 Preadipocyte Differentiation
  • Atsuko Masumi (Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Aomori University / amasumi@aomori-u.ac.jp)
Atsuko Masumi 1) , Yuko Oba 1) , Marina Tonosaki 1) , Ikumi Aizu 1) , Krisana Asano 2) , Akio Nakane 2)
1) Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Aomori University , 2) Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine
Received: May 23, 2020;   Accepted: July 09, 2020;   Released: July 20, 2020
Keywords: peroxisome proliferator-activated receptor γ, 3T3-L1 cells, thiazolidinediones, adipogenesis

Thiazolidinediones, such as troglitazone and rosiglitazone, are anti-diabetic insulin-sensitizing agents that bind to the peroxisome proliferator-activated receptor γ (PPARγ) and have potent adipogenic effects on 3T3-L1 preadipocytes. During 3T3-L1 preadipocyte differentiation, which was induced by isobutyl methylxanthine, dexamethasone, and insulin, troglitazone treatment increased lipid content and decreased PPARγ protein levels compared with DMSO-treated control cells. However, the level of CCAAT/enhancer binding protein α (C/EBPα) and C/EBPβ proteins did not decrease in troglitazone-treated cells compared with DMSO-treated cells. Real-time PCR analysis showed that PPARγ mRNA but not C/EBPα mRNA was downregulated in troglitazone-treated adipocytes, suggesting that PPARγ protein reduction occurred due to the decrease in its transcription level. Rosiglitazone treatment also increased lipid content but decreased PPARγ expression during 3T3-L1 preadipocyte differentiation. Both thiazolidinediones significantly increased the levels of adipokines such as adipocyte protein 2 (aP2) and adiponectin in 3T3-L1 adipocytes compared with that in DMSO-treated cells. We propose that thiazolidinediones are involved in adipogenic homeostasis rather than act as agonists of PPARγ during 3T3-L1 adipocyte differentiation.