Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / metabolism
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Adipogenesis / drug effects*
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Animals
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Anti-Obesity Agents / pharmacology*
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / metabolism
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Calcitriol / pharmacology*
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Cell Nucleus / metabolism
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Dishevelled Proteins
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Fatty Acid-Binding Proteins / genetics
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Fatty Acid-Binding Proteins / metabolism
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Gene Expression / drug effects
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Lipoprotein Lipase / genetics
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Lipoprotein Lipase / metabolism
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Low Density Lipoprotein Receptor-Related Protein-6 / genetics
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Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
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Mice
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Wnt Proteins / genetics
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Wnt Proteins / metabolism
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Wnt Signaling Pathway / drug effects*
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Anti-Obesity Agents
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CCAAT-Enhancer-Binding Proteins
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CEBPA protein, mouse
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Dishevelled Proteins
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Dvl2 protein, mouse
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Fabp4 protein, mouse
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Fatty Acid-Binding Proteins
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Low Density Lipoprotein Receptor-Related Protein-6
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Lrp6 protein, mouse
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PPAR gamma
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Phosphoproteins
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Wnt Proteins
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Wnt10b protein, mouse
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beta Catenin
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Lipoprotein Lipase
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Calcitriol