AZD1208, a pan‐Pim kinase inhibitor, inhibits adipogenesis and induces lipolysis in 3T3‐L1 adipocytes. Issue 4 (14th February 2018)

• Record Type: Journal Article
• Authors: Park, Yu‐Kyoung; Obiang‐Obounou, Brice Wilfried; Lee, Kyung‐Bok; Choi, Jong‐Soon; Jang, Byeong‐Churl
• Is Part Of: Journal of cellular and molecular medicine. Volume 22:Issue 4(2018)
• Page Start: 2488
• Page End: 2497
• Publication Date: 2018-02-14
• Subjects: 3T3‐L1 -- adipogenesis -- AMPK -- AZD1208 -- lipolysis; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.13559
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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. AZD1208 is a pan‐Pim kinase inhibitor and is known for its anti‐cancer activity. In this study, we investigated the effect of AZD1208 on adipogenesis and lipolysis in 3T3‐L1 cells, a murine preadipocyte cell line. AZD1208 markedly suppressed lipid accumulation and reduced triglyceride contents in differentiating 3T3‐L1 cells, suggesting the drug's anti‐adipogenic effect. On mechanistic levels, AZD1208 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, AZD1208 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, AZD1208 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 AZD1208 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.