ArticleThe Journal of clinical investigation2022
Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Secretion and transfer of adipose lipoprotein lipase utilizes neutral sphingomyelinase 2 generated exosomes.bioRxiv : the preprint server for biology · 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
- Competitive displacement of lipoprotein lipase from heparan sulfate is orchestrated by a disordered acidic cluster in GPIHBP1.Journal of lipid research · 2025Article
- A negatively charged cluster in the disordered acidic domain of GPIHBP1 provides selectivity in the interaction with lipoprotein lipase.Scientific reports · 2024Article
- Hypertriglyceridemia in Apoa5-/- mice results from reduced amounts of lipoprotein lipase in the capillary lumen.The Journal of clinical investigation · 2023Article
- The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes.Journal of diabetes investigation · 2023Review
- Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Angiopoietin-like protein 4/8 complex-mediated plasmin generation leads to cleavage of the complex and restoration of LPL activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- QnAs with Stephen G. Young.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Low circulating PCSK9 levels inFrontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
Abstract
GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.
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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.