Paalvast Yared, de Boer Jan Freark, Groen Albert K
aDepartment of Pediatrics bDepartment of Laboratory Medicine, University of Groningen, University Medical Center Groningen cDepartment of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Curr Opin Lipidol. 2017 Jun;28(3):248-254. doi: 10.1097/MOL.0000000000000415.
To discuss recent advances in research focused on intestinal lipid handling.
An important strategy in reducing atherosclerosis and risk of cardiovascular events is to increase the rate of reverse cholesterol transport, including its final step; cholesterol excretion from the body. The rate of removal is determined by a complex interplay between the factors involved in regulation of intestinal cholesterol absorption. One of these factors is a process known as transintestinal cholesterol excretion. This pathway comprises transport of cholesterol directly from the blood, through the enterocyte, into the intestinal lumen. In humans, this pathway accounts for 35% of cholesterol excretion in the feces. Mechanistic studies in mice revealed that, activation of the bile acid receptor farnesoid X receptor increases cholesterol removal via the transintestinal cholesterol excretion pathway as well as decreases plasma cholesterol and triglyceride providing an interesting target for treatment of dyslipidemia in humans. The physical chemical properties of bile acids are under control of farnesoid X receptor and determine intestinal cholesterol and triglyceride solubilization as well as absorption, providing a direct link between these two important factors in the pathogenesis of cardiovascular disease. Besides bile acids, intestinal phospholipids are important for luminal lipid solubilization. Interestingly, phospholipid remodeling through LPCAT3 was shown to be pivotal for uptake of fatty acids by enterocytes, which may provide a mechanistic handle for therapeutic intervention.
The importance of the intestine in control of cholesterol and triglyceride homeostasis is increasingly recognized. Recently, novel factors involved in regulation of cholesterol excretion and intestinal triglyceride and fatty acid uptake have been reported and are discussed in this short review.
讨论近期聚焦于肠道脂质处理的研究进展。
降低动脉粥样硬化和心血管事件风险的一项重要策略是提高逆向胆固醇转运速率，包括其最后一步，即胆固醇从体内排出。排出速率由参与调节肠道胆固醇吸收的多种因素之间复杂的相互作用决定。其中一个因素是一种称为经肠胆固醇排泄的过程。该途径包括胆固醇直接从血液通过肠上皮细胞进入肠腔的转运。在人类中，该途径占粪便中胆固醇排泄量的35%。对小鼠的机制研究表明，胆汁酸受体法尼醇X受体的激活增加了经肠胆固醇排泄途径的胆固醇清除，同时降低了血浆胆固醇和甘油三酯，为治疗人类血脂异常提供了一个有趣的靶点。胆汁酸的物理化学性质受法尼醇X受体控制，决定肠道胆固醇和甘油三酯的溶解以及吸收，在心血管疾病发病机制中的这两个重要因素之间建立了直接联系。除了胆汁酸，肠道磷脂对肠腔内脂质溶解也很重要。有趣的是，通过溶血磷脂酰胆碱酰基转移酶3进行的磷脂重塑被证明对肠上皮细胞摄取脂肪酸至关重要，这可能为治疗干预提供一个机制切入点。
肠道在控制胆固醇和甘油三酯稳态中的重要性日益受到认可。最近，有报道称发现了参与调节胆固醇排泄以及肠道甘油三酯和脂肪酸摄取的新因素，本简短综述对此进行了讨论。
