Evidence map›Paper›PMID 40112106›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

ANGPTL3/8 is an atypical unfoldase that regulates intravascular lipolysis by catalyzing unfolding of lipoprotein lipase.

Anni Kumari, Sanne W R Larsen, Signe Bondesen, Yuewei Qian, Hao D Tian, Sydney G Walker, Brandon S J Davies, Alan T Remaley, Stephen G Young, Robert J Konrad and 2 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
  2. Review
  3. GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. 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 · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. 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 · 2025
    Article
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Anni KumariFinsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen N DK-2200, Denmark.ORCID 0000-0001-8245-269X
Sanne W R LarsenFinsen Laboratory, Biotechnology Research and Innovation Centre, University of Copenhagen, Copenhagen N DK-2200, Denmark.
Signe BondesenFinsen Laboratory, Biotechnology Research and Innovation Centre, University of Copenhagen, Copenhagen N DK-2200, Denmark.
Yuewei QianLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 462585.ORCID 0000-0003-0584-4723
Hao D TianLaboratory of Lipoprotein Metabolism, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20814.
Sydney G WalkerDepartment of Biochemistry and Molecular Biology, University of Iowa, Iowa, IA 52242.
Brandon S J DaviesDepartment of Biochemistry and Molecular Biology, University of Iowa, Iowa, IA 52242.ORCID 0000-0002-7168-8522
Alan T RemaleyLaboratory of Lipoprotein Metabolism, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20814.
Stephen G YoungDepartment of Medicine, University of California, Los Angeles, CA 90095.ORCID 0000-0001-7270-3176
Robert J KonradLilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 462585.ORCID 0000-0003-0923-0542
Thomas J D JørgensenDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M DK-5320, Denmark.ORCID 0000-0002-7149-316X
Michael PlougFinsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen N DK-2200, Denmark.ORCID 0000-0003-2215-4265

Funding

Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2019 to 2023
$11.7M
Refining Physiologic Mechanisms for Intravascular Triglyceride MetabolismR01HL087228 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEIGNEUX, ANNE, FONG, LOREN GI · 2007 to 2024
$7.8M
Investigating Mechanisms for Lipid Transport in Health and DiseaseR35HL139725 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2018 to 2024
$6.1M
Regulation of Intravascular Triglyceride HydrolysisR35HL176438 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Stephen G. Young · 2025 to 2026
$2.2M
Regulation of Endothelial Lipase and HDL Metabolism by ANGPTL3R01HL162698 · NHLBI · UNIVERSITY OF IOWA · PI BRANDON Scott Joseph DAVIES · 2023 to 2026
$2.0M
Solving longstanding mysteries in plasma triglyceride metabolismR01HL171737 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANNE BEIGNEUX, Loren Gi Fong · 2024 to 2026
$1.9M
Fondation Leducq (Leducq Foundation) 23CVD02 19CVD04HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL171737 R01HL162698 R35HL139725 P01HL146358 R01HL087228NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL087228NHLBI NIH HHS R01 HL162698NHLBI NIH HHS R01 HL171737NHLBI NIH HHS R35 HL139725NHLBI NIH HHS R35 HL176438Novo Nordisk Foundation Center for Basic Metabolic Research (NovoNordisk Foundation Center for Basic Metabolic Research) NNF20OC0063444The John and Birthe Meyer Foundation 100
6 · The paper itself

Abstract

Lipoprotein lipase (LPL) carries out the lipolytic processing of triglyceride-rich lipoproteins (TRL) along the luminal surface of capillaries. LPL activity is regulated by the angiopoietin-like proteins (ANGPTL3, ANGPTL4, ANGPTL8), which control the delivery of TRL-derived lipid nutrients to tissues in a temporal and spatial fashion. This regulation of LPL mediates the partitioning of lipid delivery to adipose tissue and striated muscle according to nutritional status. A complex between ANGPTL3 and ANGPTL8 (ANGPTL3/8) inhibits LPL activity in oxidative tissues, but its mode of action has remained unknown. Here, we used biophysical techniques to define how ANGPTL3/8 and ANGPTL3 interact with LPL and how they drive LPL inactivation. We demonstrate, by mass photometry, that ANGPTL3/8 is a heterotrimer with a 2:1 ANGPTL3:ANGPTL8 stoichiometry and that ANGPTL3 is a homotrimer. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) studies revealed that ANGPTL3/8 and ANGPTL3 use the proximal portion of their N-terminal α-helices to interact with sequences surrounding the catalytic pocket in LPL. That binding event triggers unfolding of LPL's

Indexed as

Angiopoietin-like ProteinsLipolysisLipoprotein LipasePeptide HormonesProtein UnfoldingAngiopoietin-Like Protein 3Angiopoietin-Like Protein 8AnimalsHumansTriglyceridesAngiopoietin-Like Protein 3Angiopoietin-Like Protein 8Angiopoietin-like ProteinsANGPTL3 protein, humanANGPTL8 protein, humanLipoprotein LipasePeptide HormonesTriglycerideslipaselipolysistriglycerides

Identifiers

PMID40112106
PMCPMC11962473

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.