ArticleThe Journal of clinical investigation2023
Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 17 citations in OpenAlex.
- Decreases in circulating ANGPTL3/8 concentrations following retatrutide treatment parallel reductions in serum lipids.Diabetes, obesity & metabolism · 2025Trial
- Targeting the angiopoietin-like protein 3/8 complex with a monoclonal antibody in patients with mixed hyperlipidemia: a phase 1 trial.Nature medicine · 2025Trial
- PFAS Exposure and Metabolic Disorders: Mechanistic Insights into Lipid and Glucose Homeostasis.Biomolecules · 2026Review
- Effects of fenofibrate on angiopoietin-like 3/4/8 proteins and apolipoprotein A5.Journal of lipid research · 2026Article
- Unveiling novel drug targets for atherosclerosis: A Mendelian randomization analysis.Medicine · 2026Article
- Associations of ANGPTL3/4/8 proteins and complexes with heart failure and heart failure mortality.Lipids in health and disease · 2026Article
- Biomarkers of Adipose Color: A Multi-Omics Analysis Unravels the Molecular Landscape of White and Yellow Fat in Kazakh Horse.Biology · 2026Article
- A neutralizing APOA5 monoclonal antibody reduces amounts of lipoprotein lipase in capillaries and triggers hypertriglyceridemia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular characterization of a rare heterozygousFrontiers in genetics · 2026Article
- GPIHBP1, lipoprotein lipase, and triglyceride-rich lipoproteins in capillaries of the choroid plexus and circumventricular organs.The Journal of clinical investigation · 2025Article
- ANGPTL3/8 is an atypical unfoldase that regulates intravascular lipolysis by catalyzing unfolding of lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.Current atherosclerosis reports · 2024Review
- APOA5 deficiency causes hypertriglyceridemia by reducing amounts of lipoprotein lipase in capillaries.Journal of lipid research · 2024Review
- A unified model for regulating lipoprotein lipase activity.Trends in endocrinology and metabolism: TEM · 2024Review
- Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Imaging the ANGPTL3/8-mediated regulation of lipoprotein lipase in the heart.Journal of lipid research · 2023Article
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
Abstract
Why apolipoprotein AV (APOA5) deficiency causes hypertriglyceridemia has remained unclear, but we have suspected that the underlying cause is reduced amounts of lipoprotein lipase (LPL) in capillaries. By routine immunohistochemistry, we observed reduced LPL staining of heart and brown adipose tissue (BAT) capillaries in Apoa5-/- mice. Also, after an intravenous injection of LPL-, CD31-, and GPIHBP1-specific mAbs, the binding of LPL Abs to heart and BAT capillaries (relative to CD31 or GPIHBP1 Abs) was reduced in Apoa5-/- mice. LPL levels in the postheparin plasma were also lower in Apoa5-/- mice. We suspected that a recent biochemical observation - that APOA5 binds to the ANGPTL3/8 complex and suppresses its capacity to inhibit LPL catalytic activity - could be related to the low intracapillary LPL levels in Apoa5-/- mice. We showed that an ANGPTL3/8-specific mAb (IBA490) and APOA5 normalized plasma triglyceride (TG) levels and intracapillary LPL levels in Apoa5-/- mice. We also showed that ANGPTL3/8 detached LPL from heparan sulfate proteoglycans and GPIHBP1 on the surface of cells and that the LPL detachment was blocked by IBA490 and APOA5. Our studies explain the hypertriglyceridemia in Apoa5-/- mice and further illuminate the molecular mechanisms that regulate plasma TG metabolism.
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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 Socratic graph.