title: 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 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.
authors.affiliation: Department of Food and Nutrition, Korea University, 161 Jeongneung-ro, Seongbuk-gu, Seoul 136-703, South Korea.
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Suh
authors.affiliation: Department of Food and Nutrition, Korea University, 161 Jeongneung-ro, Seongbuk-gu, Seoul 136-703, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Food and Nutrition, Korea University, 161 Jeongneung-ro, Seongbuk-gu, Seoul 136-703, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 139-774, South Korea. Electronic address: sirchoi@hanmail.net.
authors.forename: Hyeon-Son
authors.initials: HS
authors.lastname: Choi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D015027:Zebrafish / Q000254:growth & development
chemical_list: D000975:Antioxidants; D022763:CCAAT-Enhancer-Binding Protein-alpha; D050556:Fatty Acid-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D047495:PPAR gamma; D012838:Silymarin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000077385:Silybin
keywords: 3T3-L1; AMPKα; Adipogenesis; Cell cycle arrest; Silibinin; Zebrafish