Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Cell Mol Gastroenterol Hepatol. 2019;7(3):487-501. doi: 10.1016/j.jcmgh.2018.10.015. Epub 2018 Nov 2.
Rapid and efficient digestion and absorption of dietary triglycerides and other lipids by the intestine, the packaging of those lipids into lipoprotein chylomicron (CM) particles, and their secretion via the lymphatic duct into the blood circulation are essential in maintaining whole-body lipid and energy homeostasis. Biosynthesis and assembly of CMs in enterocytes is a complex multistep process that is subject to regulation by intracellular signaling pathways as well as by hormones, nutrients, and neural factors extrinsic to the enterocyte. Dysregulation of this process has implications for health and disease, contributing to dyslipidemia and a potentially increased risk of atherosclerotic cardiovascular disease. There is increasing recognition that, besides intracellular regulation of CM assembly and secretion, regulation of postassembly pathways also plays important roles in CM secretion. This review examines recent advances in our understanding of the regulation of CM secretion in relation to mobilization of intestinal lipid stores, drawing particular attention to post-assembly regulatory mechanisms, including intracellular trafficking of triglycerides in enterocytes, CM mobilization from the lamina propria, and regulated transport of CM by intestinal lymphatics.
肠道内膳食三酰甘油和其他脂质的快速有效消化吸收,将这些脂质包装成乳糜微粒(CM)颗粒,并通过淋巴管分泌到血液循环中,这对维持全身脂质和能量平衡至关重要。肠细胞中 CM 的生物合成和组装是一个复杂的多步骤过程,受细胞内信号通路以及激素、营养素和肠细胞外的神经因素的调节。这一过程的失调对健康和疾病有影响,导致血脂异常,并可能增加患动脉粥样硬化性心血管疾病的风险。人们越来越认识到,除了 CM 组装和分泌的细胞内调节外,组装后途径的调节也在 CM 分泌中发挥重要作用。本文综述了我们对 CM 分泌调节的理解的最新进展,特别是在动员肠道脂质储存方面,特别关注组装后调节机制,包括肠细胞内三酰甘油的细胞内转运、从固有层中动员 CM 以及肠道淋巴管对 CM 的调节运输。