부산대학교 도서관

Several nutrients modulate the transcriptional activity of the apolipoprotein A‐I (apo A‐I) gene. To determine the influence of rare sugars on apo A‐I expression in hepatic (HepG2) and intestinal derived (Caco‐2) cell lines, apo A‐I, albumin, and SP1 were quantified with enzyme immunoassay and Western blots while mRNA levels were quantified with real‐time polymerase chain reaction. The promoter activity was measured using transient transfection assays with plasmids containing various segments and mutations in the promoter. D‐allulose and D‐tagatose, increased apo A‐I concentration in culture media while D‐sorbose and D‐allose did not have any measurable effects. D‐allulose did not increase apo A‐I levels in Caco‐2 cells. These changes paralleled the increased mRNA levels and promoter activity. D‐allulose‐response was mapped at the insulin response core element (IRCE). Mutation of the IRCE decreased the ability of D‐allulose and insulin to activate the promoter. Treatment of HepG2 cells, but not Caco‐2 cells, with D‐alluose and insulin increased SP1 expression relative to control cells. D‐allulose augmented the expression and IRCE binding of SP1, an essential transcription factor for the insulin on apo A‐I promoter activity. D‐allulose can modulate some insulin‐responsive genes and may have anti‐atherogenic properties, in part due to increasing apo A‐I production. Practical applications: Coronary artery disease (CAD) is the number one cause of mortality in industrialized countries. A risk factor associated with CAD is low high‐density lipoprotein (HDL) cholesterol and apolipoprotein A‐I (apo A‐I) concentrations in plasma. Thus, novel therapeutic agents or nutrients that upregulate apo A‐I production should be identified. D‐allulose and D‐tagatose are used as sweeteners and may have favorable effects on insulin resistance and diabetes. This study shows that D‐allulose and D‐tagatose increases apo A‐I production through increased transcription factor SP1‐binding to insulin response element of the promoter. These sweeteners modulate some insulin responsive genes, increase the production of apo‐A‐I, and therefore may have anti‐atherogenic properties. [ABSTRACT FROM AUTHOR]