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Inhibition of Lipid Accumulation and Cyclooxygenase-2 Expression in Differentiating 3T3-L1 Preadipocytes by Pazopanib, a Multikinase Inhibitor

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Author(s)
Anil Kumar YadavByeong-Churl Jang
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Int J Mol Sci
Issued Date
2021
Volume
22
Issue
9
Keyword
pazopanib3T3-L1C/EBP-αPPAR-γperilipin AAMPKCOX-2
Abstract
Pazopanib is a multikinase inhibitor with anti-tumor activity. As of now, the anti-obesity effect and mode of action of pazopanib are unknown. In this study, we investigated the effects of pazopanib on lipid accumulation, lipolysis, and expression of inflammatory cyclooxygenase (COX)-2 in differentiating and differentiated 3T3-L1 cells, a murine preadipocyte. Of note, pazopanib at 10 µM markedly decreased lipid accumulation and triglyceride (TG) content during 3T3-L1 preadipocyte differentiation with no cytotoxicity. Furthermore, pazopanib inhibited not only expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and perilipin A but also phosphorylation of signal transducer and activator of transcription (STAT)-3 during 3T3-L1 preadipocyte differentiation. In addition, pazopanib treatment increased phosphorylation of cAMP-activated protein kinase (AMPK) and its downstream effector ACC during 3T3-L1 preadipocyte differentiation. However, in differentiated 3T3-L1 adipocytes, pazopanib treatment did not stimulate glycerol release and hormone-sensitive lipase (HSL) phosphorylation, hallmarks of lipolysis. Moreover, pazopanib could inhibit tumor necrosis factor (TNF)-α-induced expression of COX-2 in both 3T3-L1 preadipocytes and differentiated cells. In summary, this is the first report that pazopanib has strong anti-adipogenic and anti-inflammatory effects in 3T3-L1 cells, which are mediated through regulation of the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT-3, ACC, perilipin A, AMPK, and COX-2.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine (의과대학)
Citation
Anil Kumar Yadav and Byeong-Churl Jang. (2021). Inhibition of Lipid Accumulation and Cyclooxygenase-2 Expression in Differentiating 3T3-L1 Preadipocytes by Pazopanib, a Multikinase Inhibitor. Int J Mol Sci, 22(9), 4884. doi: 10.3390/ijms22094884
Type
Article
ISSN
1422-0067
Source
https://www.mdpi.com/1422-0067/22/9/4884
DOI
10.3390/ijms22094884
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43807
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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