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Inhibition of adipogenesis and leptin production in 3T3-L1 adipocytes by a derivative of meridianin C

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Author(s)
Yu-Kyoung ParkTae-Yoon LeeJong-Soon ChoiVictor Sukbong HongJinho LeeJong-Wook ParkByeong-Churl Jang
Publication Year
2014
Abstract
Meridianin C, a marine alkaloid, is a potent protein kinase inhibitor and has anti-cancer activity. We have recently developed a series of meridianin C derivatives (compound 7a–7j) and reported their proviral integration Moloney Murine Leukemia Virus (pim) kinases’ inhibitory and anti-proliferative effects on human leukemia cells. Here we investigated the effect of these meridianin C derivatives on adipogenesis. Strikingly, among the derivatives tested, compound 7b most strongly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. However, meridianin C treatment was largely cytotoxic to 3T3-L1 adipocytes. On mechanistic levels, compound 7b reduced not only the expressions of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), and fatty acid synthase (FAS) but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) and STAT-5 during adipocyte differentiation. Moreover, compound 7b repressed leptin, but not adiponectin, expression during adipocyte differentiation. Collectively, these findings demonstrate that a meridianin C derivative inhibits adipogenesis by down-regulating expressions and/or phosphorylations of C/EBP-α, PPAR-γ, FAS, STAT-3 and STAT-5.

Keywords
Meridianin C derivative;
Adipogenesis;
PPAR-γ;
C/EBP-α;
STAT-3/5
Department
Dept. of Molecular Medicine (분자의학)
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.452(4) : 1078-1083, 2014
Type
Article
ISSN
0006-291X
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35151
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