Triglycerides and cholesterol circulate in the bloodstream as part of various lipoprotein particles. Three members of the angiopoietin-like (ANGPTL) protein family — ANGPTL3, ANGPTL4 and ANGPTL8 — have emerged as important regulators of plasma lipoprotein levels by inhibiting the enzyme lipoprotein lipase. Here, I review the role of ANGPTL3 in lipoprotein metabolism. In contrast to ANGPTL4 and ANGPTL8, ANGPTL3 is exclusively produced in the liver and can therefore be classified as a true hepatokine. ANGPTL3 cooperates with ANGPTL8 to inhibit lipoprotein lipase and is mostly active after feeding, whereas ANGPTL4 is mostly active after fasting. Inactivation of ANGPTL3 in mice reduces plasma triglyceride and free fatty acid levels and suppresses atherosclerosis. In humans, homozygous loss-of-function mutations in ANGPTL3 lead to low plasma levels of low-density lipoproteins, high-density lipoproteins and triglycerides, a condition referred to as familial combined hypolipidaemia. Heterozygous carriers of loss-of-function mutations in ANGPTL3 have a lower risk of coronary artery disease than non-carriers. At present, researchers are investigating antisense oligonucleotide and monoclonal antibody-based inactivation of ANGPTL3 in human clinical trials for the therapeutic management of dyslipidaemia and atherosclerosis. Thus, ANGPTL3 is an important liver-derived regulator of lipoprotein metabolism that holds considerable promise as a target for atherosclerosis.

甘油三酸酯和胆固醇作为各种脂蛋白颗粒的一部分在血液中循环。血管生成素样（ANGPTL）蛋白家族的三个成员ANGPTL3，ANGPTL4和ANGPTL8通过抑制脂蛋白脂酶成为了脂蛋白水平的重要调节剂。在这里，我回顾了ANGPTL3在脂蛋白代谢中的作用。与ANGPTL4和ANGPTL8相比，ANGPTL3仅在肝脏中产生，因此可以归类为真正的肝因子。ANGPTL3与ANGPTL8协同作用以抑制脂蛋白脂肪酶，并且在喂食后主要活跃，而ANGPTL4在禁食后主要活跃。小鼠ANGPTL3的失活降低血浆甘油三酸酯和游离脂肪酸水平，并抑制动脉粥样硬化。在人类中，ANGPTL3的纯合功能丧失突变导致低密度脂蛋白，高密度脂蛋白和甘油三酸酯的血浆水平降低，这种情况被称为家族性合并低血脂症。与非携带者相比，ANGPTL3中功能丧失突变的杂合携带者罹患冠心病的风险更低。目前，研究人员正在人类临床试验中研究血脂异常和动脉粥样硬化的反义寡核苷酸和基于单克隆抗体的ANGPTL3失活。因此，ANGPTL3是重要的肝脏衍生的脂蛋白代谢调节剂，有望作为动脉粥样硬化的靶标。