Journal
LIFE SCIENCES
Volume 135, Issue -, Pages 35-42Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2015.05.020
Keywords
3T3-L1 differentiation; Cineromycin B; GATA binding protein; Kruppel-like factor
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Aims: 3T3-L1 cells are preadipocytes and often used as a model for cellular differentiation to adipocytes; however, the mechanism of this differentiation is not completely understood even in these model cells. In this study, we sought to identify a unique anti-adipogenesis agent from microorganisms and to examine its mechanism of action to gain knowledge and create a tool and/or seed compound for anti-obesity drug discovery research. Main method: Screening for anti-adipogenesis agents from microorganisms was performed using a 3T3-L1 cell differentiation system, and an active compound was isolated. The inhibitory mechanism of the compound was investigated by measuring the expression of key regulators using quantitative real-time PCR and Western blot analysis. Key findings: The compound with anti-adipogenic activity in 3T3-L1 cells was identified as cineromycin B. Cineromycin B at 50 mu g/mL suppressed intracellular lipid accumulation and the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein alpha (C/EBP alpha.), which are master regulators of adipocyte differentiation. Further investigations showed that cineromycin B increased significantly the mRNA expression of two negative regulators of adipocyte differentiation, Kruppel-like factor (KLF) 2 and KLF3, at an early stage of the differentiation. The results of siRNA transfection experiments indicated that cineromycin B is a unique adipocyte differentiation inhibitor, acting mainly via upregulation of KLF2 and KLF3, and these KLFs may play a role in the early stage of differentiation. Significance: Cineromycin B inhibited adipocyte differentiation in 3T3-L1 cells mainly via upregulation of KLF2 and KLF3 mRNA expression at an early stage of the differentiation. (C) 2015 Elsevier Inc. All rights reserved.
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