The involvement of mitogen-activated protein kinases in the 1α,25-dihydroxy-cholecalciferol-induced inhibition of adipocyte differentiation in vitro.

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.