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Blockade of lipid accumulation by silibinin in adipocytes and zebrafish
•Silibinin inhibits adipogenesis by regulating early adipogenic factors.•Silibinin inhibits MCE during adipogenesis via cell cycle arrest.•Silibinin deactivates serine threonine-specific kinase signaling.•Silibinin activates 5′ adenosine monophosphate-activated protein kinase α signaling.•Silibinin...
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Published in: | Chemico-biological interactions 2015-02, Vol.227, p.53-62 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | •Silibinin inhibits adipogenesis by regulating early adipogenic factors.•Silibinin inhibits MCE during adipogenesis via cell cycle arrest.•Silibinin deactivates serine threonine-specific kinase signaling.•Silibinin activates 5′ adenosine monophosphate-activated protein kinase α signaling.•Silibinin inhibits lipid accumulation in zebrafish.
Silibinin is a compound present mainly in milk thistle. In this study, we investigated the mechanism by which silibinin suppresses adipogenesis of 3T3-L1 cells, and evaluated the anti-adipogenic effect of silibinin in zebrafish. Silibinin reduced lipid accumulation by downregulating adipogenic factors, such as, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer binding protein α (C/EBPα), and fatty acid-binding protein 4 (FABP4). The reduction of these adipogenic protein levels was associated with the regulation of early adipogenic factors, such as, C/EBPβ and Krüppel-like factor 2 (KLF2), and was reflected in downregulation of lipid synthetic enzymes. Silibinin arrested cells in the G0/G1 phase of the cell cycle, accompanied by downregulation of cyclins and upregulation of p27, a cell cycle inhibitor. These results correlated with the finding of deactivation of extracellular signal-regulated kinase (ERK) and AKT, a serine/threonine-specific kinase. In addition, silibinin activated AMP-activated protein kinase α (AMPKα) to inhibit fatty acid synthesis. As observed in 3T3-L1 cells, silibinin inhibited lipid accumulation in zebrafish with the reduction of adipogenic factors and triglyceride levels. Our data revealed that silibinin inhibited lipid accumulation in 3T3-L1 cells and zebrafish, and this inhibitory effect was associated with abrogation of early adipogenesis via regulation of cell cycle and AMPKα signaling. |
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ISSN: | 0009-2797 1872-7786 |
DOI: | 10.1016/j.cbi.2014.12.027 |