7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigat...7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.展开更多
AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieve...AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.展开更多
基金supported by the National Natural Science Foundation of China (32072179)Zhejiang Provincial Natural Science Foundation of China (LD21C200001)。
文摘7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.
文摘目的:探讨胆固醇结石(GS)小鼠肝脏的核受体基因——肝核受体类似物1(liver receptor homolog 1,LRH-1)及其调控基因胆固醇7α-羟化酶(cholesterol 7-αhydroxylase,CYP7A1)的表达。方法:雌性C57BL/6小鼠40只,分为2组,每组20只,分别予以正常饮食、高脂饮食喂养10周后处死。病理切片检查小鼠胆囊壁细胞组织学改变,实时定量PCR法测定肝脏LRH-1及CYP7A1表达量。Western Blot方法测定肝脏上述基因蛋白的表达量。结果:胆结石小鼠胆囊壁细胞呈现炎性改变。胆石组小鼠LRH-1 m RNA及蛋白表达均高于对照组(P<0.01),CYP7A1 m RNA及蛋白表达量较对照组升高(P<0.01)。结论:啮齿动物肝脏LRH-1和CYP7A1的表达异常与胆囊胆固醇结石形成有关,可能共同在小鼠胆结石形成中发挥作用。
基金Supported by The Medical Faculty of the Heinrich Heine University Düsseldorf
文摘AIM To compare transcriptomes of non-alcoholic fatty liver disease(NAFLD) and alcoholic liver disease(ALD) in a meta-analysis of liver biopsies.METHODS Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.RESULTS We observed predominating commonalities at the transcriptome level between ALD and NAFLD,most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction,phagosome and lysosome.However some pathways were regulated in opposite directions in ALD and NAFLD,for example,glycolysis was down-regulated in ALD and up-regulated in NAFLD.Interestingly,we found rate-limiting genes such as HMGCR,SQLE and CYP7A1 which are associated with cholesterol processes adversely regulated between ALD(down-regulated) and NAFLD(up-regulated).We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE.Additionally,we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.CONCLUSION Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile.Thus,it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile-also as possible drug targets.The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
