Abstract

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.

中文翻译：

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激素、营养素和神经网络对脂蛋白分泌的多器官协调

摘要

血浆富含甘油三酯的脂蛋白 (TRL)，尤其是致动脉粥样硬化的残余脂蛋白，会导致动脉粥样硬化性心血管疾病。高甘油三酯血症的部分原因可能是肝脏和肠道对 TRL 的分泌过多。在这里，我们专注于调节 TRL 分泌的激素、营养和神经元间通讯的复杂网络，并提供我们对这些因素相对重要性的看法。来自胰腺的激素和肽（胰岛素、胰高血糖素）、肠道 [胰高血糖素样肽 1 (GLP-1) 和 2 (GLP-2)、生长素释放肽、缩胆囊素 (CCK)、肽 YY]、脂肪组织（瘦素、脂联素) 和大脑 (GLP-1) 通过受体介导的反应和间接通过神经网络调节 TRL 分泌。此外，肠道微生物组和胆汁酸影响人类和动物模型中的脂蛋白分泌。几种营养因子通过对中枢神经系统的影响来调节肝脂蛋白的分泌。从肠道到大脑的迷走神经传入信号和从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，以影响 TRL 的分泌。其中一些因素已被广泛研究并显示出强大的监管作用，而另一些则是“新兴”监管机构，其重要性仍有待确定。这些因素相对于彼此以及相对于脂质可用性的关键调节作用的数量重要性仍然很大程度上未知。