Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Endocr Rev. 2021 Nov 16;42(6):815-838. doi: 10.1210/endrev/bnab008.
Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease. Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut [glucagon-like peptide 1 (GLP-1) and 2 (GLP-2), ghrelin, cholecystokinin (CCK), peptide YY], adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks. In addition, the gut microbiome and bile acids influence lipoprotein secretion in humans and animal models. Several nutritional factors modulate hepatic lipoprotein secretion through effects on the central nervous system. Vagal afferent signaling from the gut to the brain and efferent signals from the brain to the liver and gut are modulated by hormonal and nutritional factors to influence TRL secretion. Some of these factors have been extensively studied and shown to have robust regulatory effects whereas others are "emerging" regulators, whose significance remains to be determined. The quantitative importance of these factors relative to one another and relative to the key regulatory role of lipid availability remains largely unknown. Our understanding of the complex interorgan regulation of TRL secretion is rapidly evolving to appreciate the extensive hormonal, nutritional, and neural signals emanating not only from gut and liver but also from the brain, pancreas, and adipose tissue.
富含甘油三酯的血浆脂蛋白（TRL），尤其是致动脉粥样硬化的残粒脂蛋白，是导致心血管疾病的一个因素。高甘油三酯血症部分可能源于肝脏和肠道对 TRL 的过度分泌。本文重点关注调节 TRL 分泌的激素、营养和神经元等器官间复杂的交流网络，并阐述了这些因素的相对重要性。源于胰腺（胰岛素、胰高血糖素）、肠道[胰高血糖素样肽 1（GLP-1）和 2（GLP-2）、胃饥饿素、胆囊收缩素（CCK）、肽 YY]、脂肪组织（瘦素、脂联素）和大脑（GLP-1）的激素和肽通过受体介导的反应和间接的神经网络来调节 TRL 的分泌。此外，肠道微生物群和胆汁酸也会影响人类和动物模型中的脂蛋白分泌。一些营养因素通过对中枢神经系统的影响来调节肝脏脂蛋白的分泌。肠道到大脑的迷走传入信号以及大脑到肝脏和肠道的传出信号受到激素和营养因素的调节，从而影响 TRL 的分泌。其中一些因素已经得到了广泛的研究，并显示出了强大的调节作用，而其他因素则是“新兴”的调节剂，其意义仍有待确定。这些因素彼此之间以及与脂质可用性的关键调节作用相比，其相对重要性在很大程度上仍然未知。我们对 TRL 分泌的复杂器官间调节的理解正在迅速发展，以了解不仅来自肠道和肝脏，还来自大脑、胰腺和脂肪组织的广泛的激素、营养和神经信号。
