ArticleHeliyon2021
Angiopoietin-like protein 4 (ANGPTL4) is an inhibitor of endothelial lipase (EL) while the ANGPTL4/8 complex has reduced EL-inhibitory activity.
Article in Heliyon, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.Diabetes, obesity & metabolism · 2025Trial
- Angiopoietin-like 3 monomers are abundant in human plasma but are unable to inhibit endothelial lipase.JCI insight · 2025Article
- Metabolic reprogramming by endothelial ANGPTL4 depletion protects against diabetic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.Current medicinal chemistry · 2025Review
- A unified model for regulating lipoprotein lipase activity.Trends in endocrinology and metabolism: TEM · 2024Review
- Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins.Scientific reports · 2024Article
- Suppression of angiopoietin-like 4 reprograms endothelial cell metabolism and inhibits angiogenesis.Nature communications · 2023Article
- Genetic Mimicry Analysis Reveals the Specific Lipases Targeted by the ANGPTL3-ANGPTL8 Complex and ANGPTL4.Journal of lipid research · 2023Article
- An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif.Journal of lipid research · 2022Article
- An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues.Progress in lipid research · 2022Review
- The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously demonstrated that angiopoietin-like protein 8 (ANGPTL8) forms ANGPTL3/8 and ANGPTL4/8 complexes that increase with feeding to direct fatty acids (FA) toward adipose tissue through differential modulation of lipoprotein lipase (LPL) activity. Each complex correlated inversely with high density lipoprotein cholesterol (HDL) in control subjects. We thus investigated ANGPTL3/8 and ANGPTL4/8 levels in type 2 diabetes patients, who can present with decreased HDL. While ANGPTL3/8 levels in type 2 diabetes patients were similar to those previously observed in normal controls, ANGPTL4/8 levels were roughly twice as high as those in control subjects. Concentrations of ANGPTL3/8 and ANGPTL4/8 in type 2 diabetes patients were inversely correlated with HDL, with the correlation being significant for ANGPTL4/8. We therefore measured the ability of the various ANGPTL proteins and complexes to inhibit endothelial lipase (EL), the enzyme which hydrolyzes phospholipids (PL) in HDL. While confirming ANGPTL3 as an EL inhibitor, we found that ANGPTL4 was a more potent EL inhibitor than ANGPTL3. Interestingly, we observed that while ANGPTL3/8 had increased EL-inhibitory activity compared to ANGPTL3 alone, ANGPTL4/8 exhibited decreased potency in inhibiting EL compared to ANGPTL4 alone. Together, these results show for the first time that ANGPTL4 is a more potent EL inhibitor than ANGPTL3 and suggest a possible reason for why ANGPTL4/8 levels are correlated inversely with HDL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.