Department of Microbiology, Chung-Ang University College of Medicine, Seoul 156-756, Republic of Korea.
Int J Mol Med. 2012 Nov;30(5):1219-24. doi: 10.3892/ijmm.2012.1101. Epub 2012 Aug 20.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active metabolite of vitamin D, was found to have anti-adipogenic activity, however, its mechanism of action has not been fully elucidated. In this study, 3T3-L1 preadipocytes were differentiated in the presence and absence of 1,25(OH)2D3, and the expression of the genes and proteins of the wingless-type MMTV integration site (WNT)/β-catenin pathway were analyzed. While the expression of the members of the WNT/β-catenin pathway were significantly downregulated during the adipogenesis of untreated 3T3-L1 cells, 1,25(OH)2D3 treatment was found to maintain the WNT/β-catenin pathway. Among the members of the WNT/β-catenin pathway, the levels of WNT10B and disheveled (DVL)2 as well as the phosphorylation of glycogen synthase kinase (GSK)3β were maintained by 1,25(OH)2D3 treatment. The levels of nuclear β-catenin, which were downregulated during adipogenesis, were also maintained by 1,25(OH)2D3 treatment. The results of this study suggested that the anti-adipogenic effect of 1,25(OH)2D3 was mediated by the maintenance of the WNT/β-catenin pathway, which was normally downregulated during adipogenesis.
1,25-二羟维生素 D3（1,25(OH)2D3）是维生素 D 的活性代谢物，具有抗脂肪生成活性，但作用机制尚未完全阐明。在这项研究中，3T3-L1 前脂肪细胞在有或没有 1,25(OH)2D3 的情况下分化，并分析了 Wnt/β-catenin 通路的基因和蛋白表达。虽然在未经处理的 3T3-L1 细胞的脂肪生成过程中，Wnt/β-catenin 通路的成员表达明显下调，但 1,25(OH)2D3 处理被发现能维持 Wnt/β-catenin 通路。在 Wnt/β-catenin 通路的成员中，WNT10B 和 DVL2 的水平以及糖原合成酶激酶（GSK）3β的磷酸化水平均被 1,25(OH)2D3 处理所维持。在脂肪生成过程中下调的核 β-catenin 水平也被 1,25(OH)2D3 处理所维持。本研究结果表明，1,25(OH)2D3 的抗脂肪生成作用是通过维持 Wnt/β-catenin 通路介导的，而该通路在脂肪生成过程中通常下调。
