Blockade of lipid accumulation by silibinin in adipocytes and zebrafish

Abstract

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 gamma(PPAR gamma), CCAAT-enhancer binding protein alpha(C/EBP alpha), 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/EBP beta and Kruppel-like factor 2 (KLF2), and was reflected in downregulation of lipid synthetic enzymes. Silibinin arrested cells in the G(0)/G(1) 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 alpha(AMPK alpha) 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 AMPK alpha signaling. (C) 2014 Elsevier Ireland Ltd. All rights reserved.