ArticleBiochimica et biophysica acta2016
Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain.
Article in Biochimica et biophysica acta, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 117 citations in OpenAlex.
- Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol.Journal of cachexia, sarcopenia and muscle · 2019Trial
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- N-Arachidonoyl-phosphatidylethanolamide phospholipase D activation by muscarinic receptors.The Journal of physiology · 2026Article
- Palmitoylethanolamide in Human and Animal Obesity.Molecules (Basel, Switzerland) · 2026Review
- Regulation of Cholesterol and Triglyceride Metabolism by Fatty acid Ethanolamides.Current atherosclerosis reports · 2026Review
- The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.Cell death & disease · 2026Article
- Integrated lipidomic and transcriptomic profiling of imiquimod-induced psoriasiform dermatitis.Frontiers in cell and developmental biology · 2026Article
- Sex differences in plasma endocannabinoids and related lipids before and after single and repeated mTBI: an exploratory study of endolipid plasma biomarkers.Frontiers in molecular neuroscience · 2026Article
- FAAH and MAGL inhibition: Evolving approaches to treating substance use disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Genetic deletion of NAPE-PLD alters stress responsiveness and HPA-axis functionality in a context-dependent manner in mice.Neuropharmacology · 2025Article
- Characterization of cell-type specific knockout of different elements of the endocannabinoid system in cortical glutamatergic neurons in the context of stress-induced behavioral phenotype.Journal of cannabis research · 2025Article
- Mice lacking the endocannabinoid-synthesizing enzyme NAPE-PLD exhibit sex-dependent dysregulations in responsiveness to oxycodone and a natural reward.Neuropharmacology · 2025Article
- Sex Differences in Plasma Levels of Endocannabinoids and Related Lipids Before and After acute and repeated mTBI: an exploratory study for plasma biomarkers for mTBI.bioRxiv : the preprint server for biology · 2025Article
- Acetaminophen inhibits diacylglycerol lipase synthesis of 2-arachidonoyl glycerol: Implications for nociception.Cell reports. Medicine · 2025Article
- Article
- NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis.Molecular psychiatry · 2024Article
- Palmitoylethanolamide causes dose-dependent changes in brain function and the lipidome.Frontiers in neuroscience · 2024Article
- Imaging and Genetic Tools for the Investigation of the Endocannabinoid System in the CNS.International journal of molecular sciences · 2023Review
- Goods and Bads of the Endocannabinoid System as a Therapeutic Target: Lessons Learned after 30 Years.Pharmacological reviews · 2023Review
- Small Molecule Activation of NAPE-PLD Enhances Efferocytosis by Macrophages.ACS chemical biology · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
A leading hypothesis of N-acyl ethanolamine (NAE) biosynthesis, including the endogenous cannabinoid anandamide (AEA), is that it depends on hydrolysis of N-acyl-phosphatidylethanolamines (NAPE) by a NAPE-specific phospholipase D (NAPE-PLD). Thus, deletion of NAPE-PLD should attenuate NAE levels. Previous analyses of two different NAPE-PLD knockout (KO) strains produced contradictory data on the importance of NAPE-PLD to AEA biosynthesis. Here, we examine this hypothesis with a strain of NAPE-PLD KO mice whose lipidome is uncharacterized. Using HPLC/MS/MS, over 70 lipids, including the AEA metabolite, N-arachidonoyl glycine (NAGly), the endocannabinoid 2-arachidonyl glycerol (2-AG) and prostaglandins (PGE(2) and PGF(2α)), and over 60 lipoamines were analyzed in 8 brain regions of KO and wild-type (WT) mice. Lipidomics analysis of this third NAPE-PLD KO strain shows a broad range of lipids that were differentially affected by lipid species and brain region. Importantly, all 6 NAEs measured were significantly reduced, though the magnitude of the effect varied by fatty acid saturation length and brain region. 2-AG levels were only impacted in the brainstem, where levels were significantly increased in KO mice. Correspondingly, levels of arachidonic acid were significantly decreased exclusively in brainstem. NAGly levels were significantly increased in 4 brain regions and levels of PGE(2) increased in 6 of 8 brain regions in KO mice. These data indicate that deletion of NAPE-PLD has far broader effects on the lipidome than previously recognized. Therefore, behavioral characteristics of suppressing NAPE-PLD activity may be due to a myriad of effects on lipids and not simply due to reduced AEA biosynthesis.
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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.