Wang Fei, Kohan Alison B, Lo Chun-Min, Liu Min, Howles Philip, Tso Patrick
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237.
Department of Nutritional Sciences, University of Connecticut Advanced Technology Laboratory, Storrs, CT 06269.
J Lipid Res. 2015 Aug;56(8):1403-18. doi: 10.1194/jlr.R052753. Epub 2015 Feb 1.
The purpose of this review is to summarize our current understanding of the physiological roles of apoA-IV in metabolism, and to underscore the potential for apoA-IV to be a focus for new therapies aimed at the treatment of diabetes and obesity-related disorders. ApoA-IV is primarily synthesized by the small intestine, attached to chylomicrons by enterocytes, and secreted into intestinal lymph during fat absorption. In circulation, apoA-IV is associated with HDL and chylomicron remnants, but a large portion is lipoprotein free. Due to its anti-oxidative and anti-inflammatory properties, and because it can mediate reverse-cholesterol transport, proposed functions of circulating apoA-IV have been related to protection from cardiovascular disease. This review, however, focuses primarily on several properties of apoA-IV that impact other metabolic functions related to food intake, obesity, and diabetes. In addition to participating in triglyceride absorption, apoA-IV can act as an acute satiation factor through both peripheral and central routes of action. It also modulates glucose homeostasis through incretin-like effects on insulin secretion, and by moderating hepatic glucose production. While apoA-IV receptors remain to be conclusively identified, the latter modes of action suggest that this protein holds therapeutic promise for treating metabolic disease.
本综述的目的是总结我们目前对载脂蛋白A-IV在代谢中的生理作用的理解，并强调载脂蛋白A-IV作为针对糖尿病和肥胖相关疾病的新疗法重点的潜力。载脂蛋白A-IV主要由小肠合成，被肠细胞附着于乳糜微粒上，并在脂肪吸收过程中分泌到肠淋巴中。在循环中，载脂蛋白A-IV与高密度脂蛋白和乳糜微粒残粒相关，但很大一部分是游离脂蛋白。由于其抗氧化和抗炎特性，并且因为它可以介导胆固醇逆向转运，循环中的载脂蛋白A-IV的推测功能与预防心血管疾病有关。然而，本综述主要关注载脂蛋白A-IV的几个特性，这些特性会影响与食物摄入、肥胖和糖尿病相关的其他代谢功能。除了参与甘油三酯吸收外，载脂蛋白A-IV还可以通过外周和中枢作用途径作为急性饱腹感因子。它还通过对胰岛素分泌的肠促胰岛素样作用以及调节肝脏葡萄糖生成来调节葡萄糖稳态。虽然载脂蛋白A-IV的受体仍有待最终确定，但后一种作用模式表明这种蛋白质在治疗代谢疾病方面具有治疗前景。
