Angiopoietin-like protein 8: a multifaceted protein instrumental in regulating triglyceride metabolism.
| Autor: | Wen Y; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA., Chen YQ, Konrad RJ |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Current opinion in lipidology [Curr Opin Lipidol] 2024 Apr 01; Vol. 35 (2), pp. 58-65. Date of Electronic Publication: 2023 Nov 14. |
| DOI: | 10.1097/MOL.0000000000000910 |
| Abstrakt: | 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. (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|