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

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Author(s)
YU-KYOUNG PARK1VICTOR SUKBONG HONGTAE-YOON LEEJINHO LEEJONG-SOON CHOIDONG-SOON PARKGI-YOUNG PARKBYEONG-CHURL JANG
Keimyung Author(s)
Jang, Byeong Churl
Department
Dept. of Molecular Medicine (분자의학)
Journal Title
International Journal of Molecular Medicine
Issued Date
2016
Volume
37
Issue
1
Keyword
SGI-1776AdipogenesisPeroxisome proliferator-activated receptor-γCCAAT/enhancer-binding protein-αSignal transducer and activator of transcription-3Fatty acid synthase
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.
Keimyung Author(s)(Kor)
장병철
Publisher
School of Medicine
Citation
YU-KYOUNG PARK1 et al. (2016). The novel anti-adipogenic effect and mechanisms of action of SGI-1776, a Pim-specific inhibitor, in 3T3-L1 adipocytes. International Journal of Molecular Medicine, 37(1), 157–164. doi: 10.3892/ijmm.2015.2415
Type
Article
ISSN
1107-3756
Source
https://www.spandidos-publications.com/ijmm/37/1/157
DOI
10.3892/ijmm.2015.2415
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33313
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
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