Lo Chunmin C, Coschigano Karen T
The Diabetes Institute, Interdisciplinary Program in Molecular and Cellular Biology, and Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, United States.
Front Physiol. 2020 Jul 8;11:796. doi: 10.3389/fphys.2020.00796. eCollection 2020.
Fatty meals induce intestinal secretion of chylomicrons (CMs) containing apolipoprotein (Apo) B48. These CMs travel the lymphatic system before entering the circulation. ApoB48 is produced after post-transcriptional RNA modification by Apobec-1 editing enzyme, exclusively in the small intestine of humans and most other mammals. In contrast, in the liver where Apobec-1 editing enzyme is not expressed (except in rats and mice), the unedited transcript encodes a larger protein, ApoB100, which is used in the formation of very low-density lipoproteins (VLDL) to transport liver-synthesized fat to peripheral tissues. Apobec-1 knockout (KO) mice lack the ability to perform ApoB RNA editing, and thus, express ApoB100 in the intestine. These mice, maintained on either a chow diet or high fat diet, have body weight gain and food intake comparable to their wildtype (WT) counterparts on the respective diet; however, they secrete larger triglyceride (TG)-rich lipoprotein particles and at a slower rate than the WT mice. Using a lymph fistula model, we demonstrated that Apobec-1 KO mice also produced fewer CMs and exhibited reduced lymphatic transport of TG in response to duodenal infusion of TG at a moderate dose; in contrast, the Apobec-1 KO and WT mice had similar lymphatic transport of TG when they received a high dose of TG. Thus, the smaller, energy-saving ApoB48 appears to play a superior role in comparison with ApoB100 in the control of intestinal lipid transport in response to dietary lipid intake, at least at low to moderate lipid levels.
高脂肪餐会诱导肠道分泌含有载脂蛋白（Apo）B48的乳糜微粒（CMs）。这些CMs在进入循环系统之前先通过淋巴系统运输。ApoB48是由Apobec-1编辑酶在转录后RNA修饰后产生的，仅在人类和大多数其他哺乳动物的小肠中产生。相比之下，在不表达Apobec-1编辑酶的肝脏中（大鼠和小鼠除外），未编辑的转录本编码一种更大的蛋白质ApoB100，它用于形成极低密度脂蛋白（VLDL），将肝脏合成的脂肪运输到外周组织。Apobec-1基因敲除（KO）小鼠缺乏进行ApoB RNA编辑的能力，因此在肠道中表达ApoB1百。这些小鼠无论是维持正常饮食还是高脂饮食，其体重增加和食物摄入量与相应饮食条件下的野生型（WT）小鼠相当；然而，它们分泌的富含甘油三酯（TG）的脂蛋白颗粒更大，且速率比WT小鼠慢。使用淋巴瘘模型，我们证明，在十二指肠中等剂量注入TG时，Apobec-1 KO小鼠产生的CMs也更少，且TG的淋巴运输减少；相比之下，当接受高剂量TG时，Apobec-1 KO小鼠和WT小鼠的TG淋巴运输相似。因此，至少在低至中等脂质水平下，较小的、节能的ApoB48在响应饮食脂质摄入控制肠道脂质运输方面似乎比ApoB100发挥更优的作用。
