Nauli Andromeda M, Nassir Fatiha, Zheng Shuqin, Yang Qing, Lo Chun-Min, Vonlehmden Sarah B, Lee Dana, Jandacek Ronald J, Abumrad Nada A, Tso Patrick
Department of Pathology and Laboratory Medicine, Genome Research Institute, University of Cincinnati College of Medicine, 2120 Galbraith Road, Cincinnati, OH 45237, USA.
Gastroenterology. 2006 Oct;131(4):1197-207. doi: 10.1053/j.gastro.2006.08.012. Epub 2006 Aug 16.
BACKGROUND & AIMS: Studies are aimed to determine the role of CD36 in intestinal lipid absorption.
Knock-out (KO) and wild-type (WT) lymph fistula mice were used to study fatty acids (FA) and cholesterol uptake, and chylomicron formation and secretion. Uptake of FA and cholesterol was studied by using sucrose polybehenate and fecal dual isotope methods, respectively.
The CD36 KO exhibited significant accumulation of dietary cholesterol in the intestinal lumen at the end of 6-hour lipid infusion and significant reduction of dietary cholesterol transport into the lymph. Fecal dual isotope studies, however, did not show any significant difference in cholesterol uptake, suggesting that given sufficient time, the KO intestine could compensate for the reduced cholesterol uptake observed in the acute lymph fistula studies. Recovery of dietary FA in the intestinal lumen was comparable between WT and KO, consistent with the sucrose polybehenate study. However, the KO mice accumulated more, albeit not significantly, dietary triacylglycerols in the intestine, followed by a significant reduction in lymphatic transport. The ratio of intestinal dietary triacylglycerols to FA was not higher in WT than KO, arguing against impaired lipid esterification. It is rather a deficiency in the formation and secretion of chylomicrons, as supported by the significantly less apolipoprotein B-48 and the smaller, albeit not significantly, lipoprotein particles secreted into the lymph of the KO.
CD36 may play an important role in chylomicron formation and secretion and may also facilitate cholesterol uptake in the proximal intestine.
本研究旨在确定CD36在肠道脂质吸收中的作用。
采用基因敲除(KO)和野生型(WT)淋巴瘘小鼠来研究脂肪酸(FA)和胆固醇的摄取,以及乳糜微粒的形成和分泌。分别使用蔗糖多山嵛酸酯和粪便双同位素方法研究FA和胆固醇的摄取。
在6小时脂质输注结束时,CD36基因敲除小鼠的肠腔内出现膳食胆固醇的显著蓄积,且膳食胆固醇向淋巴的转运显著减少。然而,粪便双同位素研究未显示胆固醇摄取有任何显著差异,这表明在给予足够时间的情况下,基因敲除小鼠的肠道能够弥补急性淋巴瘘研究中观察到的胆固醇摄取减少。野生型和基因敲除小鼠肠腔内膳食FA的回收率相当,这与蔗糖多山嵛酸酯研究结果一致。然而,基因敲除小鼠在肠道中蓄积了更多(尽管不显著)的膳食三酰甘油,随后淋巴转运显著减少。野生型小鼠肠道膳食三酰甘油与FA的比值并不高于基因敲除小鼠,这与脂质酯化受损的观点相悖。实际上,这是乳糜微粒形成和分泌的缺陷,基因敲除小鼠分泌到淋巴中的载脂蛋白B-48显著减少以及脂蛋白颗粒虽小但不显著可作为佐证。
CD36可能在乳糜微粒的形成和分泌中起重要作用,也可能促进近端肠道对胆固醇 的摄取。