Nutrition Research Division, Food Directorate, Health Products and Food Branch, Health Canada, Banting Research Centre, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, Canada.
Ann Nutr Metab. 2009;55(4):341-50. doi: 10.1159/000252350. Epub 2009 Oct 23.
BACKGROUND/AIMS: We elucidated the molecular mechanism(s) underlying sterol trafficking by investigating alterations in gene expression in response to increased retention of dietary phytosterols and phytostanols in stroke-prone spontaneously hypertensive (SHRSP) and normotensive Wistar Kyoto (WKY) inbred rats.
SHRSP and WKY inbred rats were fed a control diet or a diet supplemented with phytosterols or phytostanols (2 g/kg diet).
Intake of phytosterols and phytostanols increased their incorporation in plasma, red blood cells, liver, aorta and kidney, but decreased cholesterol levels in liver and aorta in both rat strains. Phytosterol intake up-regulated mRNA expression of intestinal Npc1l1 and Abcg8, and hepatic Abcg5, Abca1, Cyp27a1 and Hmgcr. Phytostanol intake up-regulated Npc1l1 and Srebp2, but down-regulated Abcg5 mRNA expression in small intestine. Phytostanols also up-regulated Abca1 expression in SHRSP rats, but down-regulated Abca1 expression in WKY inbred rats. Compared to phytosterols, dietary phytostanols reduced phytosterol levels in plasma, red blood cells, and kidney, as well as altered mRNA levels of hepatic Abca1,Cyp27a1, and Hmgcr and intestinal Abcg5/8, Hmgcr and Srebp2.
Altered expression of multiple sterol-regulatory genes may contribute to the incorporation and cholesterol-lowering actions of phytosterols and phytostanols. Phytosterols and phytostanols may act through different mechanism(s) on cholesterol and phytosterol/phytostanol trafficking.
背景/目的：我们通过研究自发性高血压卒中倾向（SHRSP）和正常血压 Wistar Kyoto（WKY）近交系大鼠对饮食中植物甾醇和植物甾烷醇保留增加的基因表达变化，阐明了甾醇转运的分子机制。
SHRSP 和 WKY 近交系大鼠喂食对照饮食或添加植物甾醇或植物甾烷醇（2 g/kg 饮食）的饮食。
植物甾醇和植物甾烷醇的摄入增加了它们在血浆、红细胞、肝脏、主动脉和肾脏中的掺入，但降低了两种大鼠肝脏和主动脉中的胆固醇水平。植物甾醇的摄入上调了肠道 NPC1L1 和 ABCG8，以及肝脏 ABCG5、ABCA1、CYP27A1 和 HMGCR 的 mRNA 表达。植物甾烷醇摄入上调了小肠 NPC1L1 和 SREBP2，但下调了小肠 ABCG5 的 mRNA 表达。植物甾烷醇还上调了 SHRSP 大鼠的 ABCA1 表达，但下调了 WKY 近交系大鼠的 ABCA1 表达。与植物甾醇相比，饮食中的植物甾烷醇降低了血浆、红细胞和肾脏中的植物甾醇水平，以及肝脏 ABCA1、CYP27A1 和 HMGCR 和肠道 ABCG5/8、HMGCR 和 SREBP2 的 mRNA 水平。
多种甾醇调节基因的表达改变可能有助于植物甾醇和植物甾烷醇的掺入和降胆固醇作用。植物甾醇和植物甾烷醇可能通过不同的机制作用于胆固醇和植物甾醇/植物甾烷醇的转运。
