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美国卫生研究院文献>Journal of Lipid Research
>Intestinal de novo phosphatidylcholine synthesis is required for dietary lipid absorption and metabolic homeostasis
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Intestinal de novo phosphatidylcholine synthesis is required for dietary lipid absorption and metabolic homeostasis
De novo phosphatidylcholine (PC) synthesis via CTP:phosphocholine cytidylyltransferase-α (CTα) is required for VLDL secretion. To determine the precise role of de novo PC synthesis in intestinal lipid metabolism, we deleted CTα exclusively in the intestinal epithelium of mice (CTαIKO mice). When fed a chow diet, CTαIKO mice showed normal fat absorption despite a ∼30% decrease in intestinal PC concentrations relative to control mice, suggesting that biliary PC can fully support chylomicron secretion under these conditions. However, when fed a high-fat diet, CTαIKO mice showed impaired passage of FAs and cholesterol from the intestinal lumen into enterocytes. Impaired intestinal lipid uptake in CTαIKO mice was associated with lower plasma triglyceride concentrations, higher plasma glucagon-like peptide 1 and peptide YY, and disruption of intestinal membrane lipid transporters after a high-fat meal relative to control mice. Unexpectedly, biliary bile acid and PC secretion was enhanced in CTαIKO mice due to a shift in expression of bile-acid transporters to the proximal intestine, indicative of accelerated enterohepatic cycling. These data show that intestinal de novo PC synthesis is required for dietary lipid absorption during high-fat feeding and that the reacylation of biliary lyso-PC cannot compensate for loss of CTα under these conditions.
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机译:VLDL分泌需要通过CTP:磷脂酰胆碱基转移酶-α(CTα)合成从头磷脂酰胆碱(PC)。为了确定从头合成PC在肠道脂质代谢中的确切作用,我们仅在小鼠(CTα IKO sup>小鼠)的肠上皮中删除了CTα。当喂以低脂饮食时,尽管肠内PC浓度相对于对照组小鼠降低了约30%,但CTα IKO sup>小鼠仍显示出正常的脂肪吸收,表明胆汁PC可以在这些条件下完全支持乳糜微粒的分泌。但是,当以高脂饮食喂养时,CTα IKO sup>小鼠显示出FAs和胆固醇从肠腔进入肠上皮细胞的途径受损。与对照相比,高脂餐后CTα IKO sup>小鼠肠道脂质摄取受损与血浆甘油三酸酯浓度降低,血浆胰高血糖素样肽1和YY肽含量升高以及肠膜脂质转运蛋白的破坏有关。老鼠。出乎意料的是,CTα IKO sup>小鼠的胆汁胆汁酸和PC分泌增加,这是由于胆汁酸转运蛋白向近端小肠的表达转移,提示肠肝循环加快。这些数据表明,在高脂喂养期间,从头开始进行PC合成对于饮食中的脂质吸收是必需的,并且胆汁溶血PC的再酰化不能补偿这些条件下CTα的损失。
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