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LY3009120, a pan-Raf kinase inhibitor, inhibits adipogenesis of 3T3-L1 cells by controlling the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT‑3, FAS, ACC, perilipin A, and AMPK.

Abstract：

:Excessive preadipocyte differentiation/adipogenesis is closely linked to the development of obesity. LY3009120 is a pan‑Raf kinase inhibitor and is known for its anticancer activities. In the present study, the effect of LY3009120 on 3T3‑L1 cell adipogenesis was investigated. The differentiation of 3T3‑L1 preadipocytes into adipocytes was measured by Oil Red O staining and AdipoRed assay. Changes of cellular protein expression and phosphorylation levels in differentiating 3T3‑L1 preadipocytes in the absence or presence of LY3009120 were determined by western blotting analysis. Cell count assay was used to assess the cytotoxicity of LY3009120 on 3T3‑L1 cells. At 0.3 µM, LY3009120 markedly inhibited lipid accumulation and decreased triglyceride content in differentiating 3T3‑L1 cells. However, it had minimal effect on the elevated expression and phosphorylation of three Raf kinase isoforms (C‑Raf, A‑Raf, and B‑Raf) observed in the cells. LY3009120 reduced not only the expression of 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, but also reduced the phosphorylation of signal transducer and activator of transcription‑3 (STAT‑3) in differentiating 3T3‑L1 cells. LY3009120 also increased the phosphorylation of adenosine 3',5'‑cyclic monophosphate (cAMP)‑activated protein kinase (AMPK), but did not affect the phosphorylation or expression of liver kinase B1 in these cells. In summary, this is the first report, to the best of our knowledge, demonstrating that LY3009120 has an anti‑adipogenic effect on 3T3‑L1 cells, which may be mediated through control of the expression and phosphorylation of C/EBP‑α, PPAR‑γ, STAT‑3, FAS, ACC, perilipin A, and AMPK.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Yang SM,Park YK,Kim JI,Lee YH,Lee TY,Jang BC

doi

10.3892/ijmm.2018.3890

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

3477-3484

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

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LY3009120, a pan-Raf kinase inhibitor, inhibits adipogenesis of 3T3-L1 cells by controlling the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT‑3, FAS, ACC, perilipin A, and AMPK.