安格普特4
脂蛋白脂酶
脂肪组织
内分泌学
脂质代谢
内科学
脂肪生成
甘油三酯
化学
白色脂肪组织
生物化学
生物
医学
胆固醇
基因
作者
Yumei Wen,Yanqun Chen,Robert J. Konrad
出处
期刊:Current Opinion in Lipidology
[Ovid Technologies (Wolters Kluwer)]
日期:2023-11-15
标识
DOI:10.1097/mol.0000000000000910
摘要
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.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).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.
科研通智能强力驱动
Strongly Powered by AbleSci AI