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Abstract
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate various genes involved in cholesterol and fatty acid synthesis. In this study, we describe that naturally occurring isothiocyanate sulforaphane (SFaN) impairs fatty acid synthase promoter activity and reduces SREBP target gene (e.g., fatty acid synthase and acetyl-CoA carboxylase 1) expression in human hepatoma Huh-7 cells. SFaN reduced SREBP proteins by promoting the degradation of the SREBP precursor. Amino acids 595–784 of SREBP-1a were essential for SFaN-mediated SREBP-1a degradation. We also found that such SREBP-1 degradation occurs independently of the SREBP cleavage-activating protein and the Keap1-Nrf2 pathway. This study identifies SFaN as an SREBP inhibitor and provides evidence that SFaN could have major potential as a pharmaceutical preparation against hepatic steatosis and obesity.
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Details
1 The University of Tokyo, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X)
2 Tokyo University of Agriculture, Department of Agricultural Chemistry, Faculty of Applied Biosciences, Tokyo, Japan (GRID:grid.410772.7) (ISNI:0000 0001 0807 3368)
3 The University of Tokyo, Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); National Taiwan University, Department of Horticulture and Landscape Architecture, College of Bioresources and Agriculture, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241)
4 Tokyo University of Agriculture, Department of Chemistry for Life Sciences and Agriculture, Tokyo, Japan (GRID:grid.410772.7) (ISNI:0000 0001 0807 3368)