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The Receptor Tyrosine Kinase c-Met Promotes Lipid Accumulation in 3T3-L1 Adipocytes

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Author(s)
Yu-Kyoung ParkByeong-Churl Jang
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
Int J Mol Sci
Issued Date
2023
Volume
24
Issue
9
Keyword
3T3-L1AMPKJNJ38877605c-Metlipid accumulation
Abstract
The receptor tyrosine kinase c-Met is elaborated in embryogenesis, morphogenesis, metabolism, cell growth, and differentiation. JNJ38877605 (JNJ) is an inhibitor of c-Met with anti-tumor activity. The c-Met expression and its role in adipocyte differentiation are unknown. Here, we investigated the c-Met expression and phosphorylation, knockdown (KD) effects, and pharmacological inhibition of c-Met by JNJ on fat accumulation in murine preadipocyte 3T3-L1 cells. During 3T3-L1 preadipocyte differentiation, strikingly, c-Met expression at the protein and mRNA levels and the protein phosphorylation on Y1234/1235 and Y1349 is crucial for inducing its kinase catalytic activity and activating a docking site for signal transducers were increased in a time-dependent manner. Of note, JNJ treatment at 20 μM that strongly inhibits c-Met phosphorylation without altering its total expression resulted in less lipid accumulation and triglyceride (TG) content with no cytotoxicity. JNJ further reduced the expression of adipogenic regulators, including CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), and perilipin A. Moreover, JNJ treatment increased cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) phosphorylation but decreased ATP levels. Significantly, KD of c-Met suppressed fat accumulation and triglyceride (TG) quantity and reduced the expression of C/EBP-α, PPAR-γ, FAS, ACC, and perilipin A. Collectively, the present results demonstrate that c-Met is a novel, highly conserved mediator of adipogenesis regulating lipid accumulation in murine adipocytes.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1422-0067
Source
https://www.mdpi.com/1422-0067/24/9/8086
DOI
10.3390/ijms24098086
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44982
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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