ArticleOncotarget2017
Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 66 citations in OpenAlex.
- Zinc accumulation in macrophages exacerbates metabolic dysfunction-associated steatotic liver disease progression.Signal transduction and targeted therapy · 2026Article
- Reorganization of Innate Immune Cell Lipid Profiles by Bioinspired Meroterpenoids to Limit Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Secreted enzyme uptake masks the in vivo phenotype of macrophage-specific lysosomal acid lipase deletion.Molecular metabolism · 2026Article
- Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue.Cell death & disease · 2025Article
- Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer.Communications medicine · 2025Article
- Autophagy and Its Association with Macrophages in Clonal Hematopoiesis Leading to Atherosclerosis.International journal of molecular sciences · 2025Review
- Cellular Uptake and Trafficking of Lipid Nanocarriers Using High-Resolution Electron Microscopy.AAPS PharmSciTech · 2025Article
- Lipid droplets in central nervous system and functional profiles of brain cells containing lipid droplets in various diseases.Journal of neuroinflammation · 2025Review
- From LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Article
- Lysosomal acid lipase A modulates leukemia stem cell response to venetoclax/tyrosine kinase inhibitor combination therapy in blast phase chronic myeloid leukemia.Haematologica · 2025Article
- In Silico Analysis Revealed Marco (SR-A6) and Abca1/2 as Potential Regulators of Lipid Metabolism in M1 Macrophage Hysteresis.International journal of molecular sciences · 2024Article
- Article
- Recent insights into lysosomal acid lipase deficiency.Trends in molecular medicine · 2023Review
- Visualizing drug-induced lipid accumulation in lysosomes of live cancer cells with stimulated Raman imaging.Biomedical optics express · 2023Article
- Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death.Frontiers in cell and developmental biology · 2023Review
- Off-target effects of the lysosomal acid lipase inhibitors Lalistat-1 and Lalistat-2 on neutral lipid hydrolases.Molecular metabolism · 2022Article
- Lipid Droplets, Phospholipase ABiomedicines · 2021Review
- Lipolysis: cellular mechanisms for lipid mobilization from fat stores.Nature metabolism · 2021Review
- Article
- Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Degradation of lysosomal lipids requires lysosomal acid lipase (LAL), the only intracellular lipase known to be active at acidic pH. We found LAL to be expressed in murine immune cells with highest mRNA expression in macrophages and neutrophils. Furthermore, we observed that loss of LAL in mice caused lipid accumulation in white blood cells in the peripheral circulation, which increased in response to an acute inflammatory stimulus. Lal-deficient (-/-) macrophages accumulate neutral lipids, mainly cholesteryl esters, within lysosomes. The cholesteryl ester fraction is particularly enriched in the PUFAs 18:2 and 20:4, important precursor molecules for lipid mediator synthesis. To investigate whether loss of LAL activity affects the generation of lipid mediators and to eliminate potential systemic effects from other cells and tissues involved in the pronounced phenotype of Lal-/- mice, we treated macrophages from Wt mice with the LAL-specific inhibitor LAListat-2. Acute inhibition of LAL resulted in reduced release of 18:2- and 20:4-derived mediators from macrophages, indicating that lipid hydrolysis by LAL is an important source for lipid mediator synthesis in macrophages. We conclude that lysosomes should be considered as organelles that provide precursor molecules for lipid mediators such as eicosanoids.
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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.