title: Cholecalciferol inhibits lipid accumulation by regulating early adipogenesis in cultured adipocytes and zebrafish.
abstract: Cholecalciferol (CCF) is a common dietary supplement as a precursor of active vitamin D. In the present study, the effect of CCF on lipid accumulation was investigated in adipocyte cells and zebrafish models. CCF effectively inhibited lipid accumulation in both experimental models; this effect was attributed to the CCF-mediated regulation of early adipogenic factors. CCF down-regulated the expressions of CCAAT-enhancer-binding protein-β (C/EBPβ), C/EBPδ, Krueppel-like factor (KLF) 4, and KLF5, while KLF2, a negative adipogenic regulator, was increased by CCF treatment. CCF inhibited cell cycle progression of adipocytes through down-regulation of cyclin A and cyclinD; p-Rb was suppressed by CCF, but p27 was up-regulated with CCF treatment. This CCF-mediated inhibition of cell cycle progression is highly correlated to the inhibitions of extracellular signal-regulated kinase (ERK), serine threonine-specific kinase (AKT), and mammalian target of rapamycin (mTOR). Furthermore, CCF-induced inactivation of acetyl-CoA carboxylase (ACC), a fatty acid synthetic enzyme, with the activation of AMP-activated protein kinase α (AMPKα) was also observed. Consistent with the observations in adipocytes, CCF effectively inhibited lipid accumulation with the down-regulation of adipogenic factors in zebrafish. The present study indicates that CCF showed anti-adipogenic effect in adipocytes and zebrafish, and its inhibitory effect was involved in the regulation of early adipogenic events including cell cycle arrest and activation of AMPKα signaling.
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 139-774, South Korea.
authors.forename: Joo Hyoun
authors.initials: JH
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.
authors.forename: Smee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 139-774, South Korea.
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Jung
authors.affiliation: Department of Food Science and Technology, Seoul Women's University, 621 Hwarang-ro, Nowon-gu, Seoul 139-774, South Korea. Electronic address: hschoi@swu.ac.kr.
authors.forename: Hyeon-Son
authors.initials: HS
authors.lastname: Choi
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D015027:Zebrafish / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D002762:Cholecalciferol
keywords: 3T3-L1; AMPKα; Adipogenesis; Cell cycle arrest; Cholecalciferol; Zebrafish