Open AccessAZD1208, a pan‐Pim kinase inhibitor, inhibits adipogenesis and induces lipolysis in 3T3‐L1 adipocytes
Author(s) -
Park YuKyoung,
ObiangObounou Brice Wilfried,
Lee KyungBok,
Choi JongSoon,
Jang ByeongChurl
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13559
Subject(s) - perilipin , lipolysis , adipogenesis , 3t3 l1 , kinase , phosphorylation , ampk , protein kinase a , chemistry , fatty acid synthase , adipocyte , lipid droplet , microbiology and biotechnology , adipose triglyceride lipase , endocrinology , medicine , biology , lipid metabolism , biochemistry , adipose tissue
The proviral integration moloney murine leukaemia virus (Pim) kinases, consisting of Pim‐1, Pim‐2 and Pim‐3, are involved in the control of cell growth, metabolism and differentiation. Pim kinases are emerging as important mediators of adipocyte differentiation. AZD 1208 is a pan‐Pim kinase inhibitor and is known for its anti‐cancer activity. In this study, we investigated the effect of AZD 1208 on adipogenesis and lipolysis in 3T3‐L1 cells, a murine preadipocyte cell line. AZD 1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3‐L1 cells, suggesting the drug's anti‐adipogenic effect. On mechanistic levels, AZD 1208 reduced not only the expressions 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 the phosphorylation of signal transducer and activator of transcription‐3 ( STAT ‐3) in differentiating 3T3‐L1 cells. Remarkably, AZD 1208 increased cAMP ‐activated protein kinase ( AMPK ) and LKB ‐1 phosphorylation while decreased intracellular ATP contents in differentiating 3T3‐L1 cells. Furthermore, in differentiated 3T3‐L1 adipocytes, AZD 1208 also partially promoted lipolysis and enhanced the phosphorylation of hormone‐sensitive lipase ( HSL ), a key lipolytic enzyme, indicating the drug's HSL ‐dependent lipolysis. In summary, the findings show that AZD 1208 has anti‐adipogenic and lipolytic effects on 3T3‐L1 adipocytes. These effects are mediated by the expression and/or phosphorylation levels of C/ EBP ‐α, PPAR ‐γ, FAS , ACC , perilipin A, STAT ‐3, AMPK and HSL .