The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes

Park,Yu-Kyoung; Hong,Victor  Sukbong; Lee,Tae-Yoon; Lee,Jinho; Choi,Jong-Soon; Park,Dong-Soon; Park,Gi-Young; Jang,Byeong-Churl

doi:10.3892/ijmm.2015.2415

The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes

Authors:
- Yu-Kyoung Park
- Victor Sukbong Hong
- Tae-Yoon Lee
- Jinho Lee
- Jong-Soon Choi
- Dong-Soon Park
- Gi-Young Park
- Byeong-Churl Jang
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Affiliations: Department of Molecular Medicine, College of Medicine, Keimyung University, Daegu 704-701, Republic of Korea, Department of Chemistry, College of Natural Sciences, Keimyung University, Daegu 704-701, Republic of Korea, Department of Microbiology, College of Medicine, Yeungnam University, Daegu 705‑717, Republic of Korea, Division of Life Science, Korea Basic Science Institute, Daejeon 305-333, Republic of Korea, Department of Rehabilitation Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea
Published online on: November 19, 2015 https://doi.org/10.3892/ijmm.2015.2415
Pages: 157-164

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Abstract

The proviral integration site for moloney murine leukemia virus (Pim) kinases, consisting of Pim-1, Pim-2 and Pim-3, belongs to a family of serine/threonine kinases that are involved in controlling cell growth and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. SGI-1776, an inhibitor of Pim kinases, is widely used to assess the physiological roles of Pim kinases, particularly cell functions. In the present study, we examined the effects of SGI-1776 on adipogenesis. The anti‑adipogenic effect of SGI‑1776 was measured by Oil Red O staining and AdipoRed assays. The effect of SGI‑1776 on the growth of 3T3‑L1 adipocytes was determined by cell count analysis. The effects of SGI‑1776 on the protein and mRNA expression of adipogenesis-related proteins and adipokines in 3T3‑L1 adipocytes were also evaluated by western blot analysis and RT‑PCR, respectively. Notably, SGI-1776 markedly inhibited lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On a mechanistic level, SGI-1776 inhibited not only the expression 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 of signal transducer and activator of transcription-3 (STAT-3). Moreover, SGI-1776 decreased the expression of adipokines, including the expression of leptin and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. These findings demonstrate that SGI-1776 inhibits adipogenesis by downregulating the expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS and STAT-3.

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