title: The involvement of mitogen-activated protein kinases in the 1α,25-dihydroxy-cholecalciferol-induced inhibition of adipocyte differentiation in vitro.
abstract: The present study was undertaken to investigate the mechanism by which 1α, 25-dihydroxy-cholecalciferol [1α,25-(OH)₂-VD₃] modulates the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes. Treatment with 1α,25-(OH)₂-VD₃ in the presence of insulin, dexamethasone and 3-isobutyl-1-methyl-xanthine significantly inhibited the triacylglycerol accumulation, and mRNA expressions of adipocytokines (adiponectin and tumor necrosis factor-α) and plasminogen activator inhibitor-1 in the pico-nanomolar concentration range, indicating that 1α,25-(OH)₂-VD₃ under physiological conditions inhibits the differentiation of 3T3-L1 cells. 1α,25-(OH)₂-VD₃ potently reduced the mRNA and/or protein expressions of CCAAT-enhancer binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), and the nuclear translocation of PPARγ. Furthermore, it inhibited the mRNA expression and phosphorylation of extracellular signal-regulated kinase (ERK), one of mitogen-activated protein kinases. These results indicate that 1α,25-(OH)₂-VD₃ can be an inhibitor of adipocyte differentiation, and suggest, in addition to C/EBPα and PPARγ, an important role of ERK in mediating 1α,25-(OH)₂-VD₃-induced alteration in adipocyte differentiation.
authors.affiliation: Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sakuma
authors.forename: Junji
authors.initials: J
authors.lastname: Fujisawa
authors.forename: Maki
authors.initials: M
authors.lastname: Sumida
authors.forename: Mami
authors.initials: M
authors.lastname: Tanigawa
authors.forename: Rie
authors.initials: R
authors.lastname: Inoda
authors.forename: Takuya
authors.initials: T
authors.lastname: Sujihera
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kohda
authors.forename: Yohko
authors.initials: Y
authors.lastname: Fujimoto
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D002117:Calcitriol