Angiopoietin-like protein 8: a multifaceted protein instrumental in regulating triglyceride metabolism.

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in lipidology Pub Date : 2024-04-01 Epub Date: 2023-11-14 DOI:10.1097/MOL.0000000000000910

Yi Wen, Yan Q Chen, Robert J Konrad

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引用次数: 0

Abstract

Purpose of review: The angiopoietin-like (ANGPTL) proteins ANGPTL3 and ANGPTL4 are critical lipoprotein lipase (LPL) inhibitors. This review discusses the unique ability of the insulin-responsive protein ANGPTL8 to regulate triglyceride (TG) metabolism by forming ANGPTL3/8 and ANGPTL4/8 complexes that control tissue-specific LPL activities.

Recent findings: After feeding, ANGPTL4/8 acts locally in adipose tissue, has decreased LPL-inhibitory activity compared to ANGPTL4, and binds tissue plasminogen activator (tPA) and plasminogen to generate plasmin, which cleaves ANGPTL4/8 and other LPL inhibitors. This enables LPL to be fully active postprandially to promote efficient fatty acid (FA) uptake and minimize ectopic fat deposition. In contrast, liver-derived ANGPTL3/8 acts in an endocrine manner, has markedly increased LPL-inhibitory activity compared to ANGPTL3, and potently inhibits LPL in oxidative tissues to direct TG toward adipose tissue for storage. Circulating ANGPTL3/8 levels are strongly correlated with serum TG, and the ANGPTL3/8 LPL-inhibitory epitope is blocked by the TG-lowering protein apolipoprotein A5 (ApoA5).

Summary: ANGPTL8 plays a crucial role in TG metabolism by forming ANGPTL3/8 and ANGPTL4/8 complexes that differentially modulate LPL activities in oxidative and adipose tissues respectively. Selective ANGPTL8 inhibition in the context of the ANGPTL3/8 complex has the potential to be a promising strategy for treating dyslipidemia.

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血管生成素样蛋白8:调节甘油三酯代谢的多方面蛋白。

综述目的:血管生成素样(ANGPTL)蛋白ANGPTL3和ANGPTL4是重要的脂蛋白脂肪酶(LPL)抑制剂。本文讨论了胰岛素反应蛋白ANGPTL8通过形成控制组织特异性LPL活性的ANGPTL3/8和ANGPTL4/8复合物来调节甘油三酯(TG)代谢的独特能力。近期研究发现:摄食后，ANGPTL4/8在脂肪组织中局部作用，与ANGPTL4相比，抑制LPL活性降低，并结合组织纤溶酶原激活物(tPA)和纤溶酶原生成纤溶酶，从而裂解ANGPTL4/8等LPL抑制剂。这使得LPL在餐后充分活跃，以促进有效的脂肪酸(FA)摄取和减少异位脂肪沉积。相比之下，肝脏来源的ANGPTL3/8以内分泌方式起作用，与ANGPTL3相比，其抑制LPL的活性显著增加，并能有效抑制氧化组织中的LPL，使TG直接进入脂肪组织储存。循环ANGPTL3/8水平与血清TG密切相关，ANGPTL3/8 lpl抑制表位被降TG蛋白载脂蛋白A5 (ApoA5)阻断。摘要:ANGPTL8通过形成ANGPTL3/8和ANGPTL4/8复合物，分别在氧化组织和脂肪组织中差异调节LPL活性，在TG代谢中起着至关重要的作用。在ANGPTL3/8复合物的背景下，选择性抑制ANGPTL8有可能成为治疗血脂异常的一种有前途的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.