ArticlePloS one2015
Fever Is Mediated by Conversion of Endocannabinoid 2-Arachidonoylglycerol to Prostaglandin E2.
Article in PloS one, 2015. 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, 32 citations in OpenAlex.
- Immune-modulating effects of dietary cannabinoid-receptor 2 agonist beta-caryophyllene and cooling frequency in dairy cows under environmental heat load.Frontiers in immunology · 2026Article
- Pathophysiology of Fever and Application of Infrared Thermography (IRT) in the Detection of Sick Domestic Animals: Recent Advances.Animals : an open access journal from MDPI · 2021Review
- Antiplasmodial, antinociceptive and antipyretic potential of the stem bark extract ofJournal of traditional and complementary medicine · 2021Article
- LimeMap: a comprehensive map of lipid mediator metabolic pathways.NPJ systems biology and applications · 2021Article
- Review
- Delayed Fever and Acute Kidney Injury in Patients with Urinary Tract Infection.Journal of clinical medicine · 2020Article
- Roles of polyunsaturated fatty acids, from mediators to membranes.Journal of lipid research · 2020Review
- Druggable Targets in Endocannabinoid Signaling.Advances in experimental medicine and biology · 2020Review
- Endocannabinoids and relatedInflammation and regeneration · 2018Review
- Lipoquality control by phospholipase AProceedings of the Japan Academy. Series B, Physical and biological sciences · 2017Review
- Fhf2 gene deletion causes temperature-sensitive cardiac conduction failure.Nature communications · 2016Article
- MicroRNA-21 regulates prostaglandin E2 signaling pathway by targeting 15-hydroxyprostaglandin dehydrogenase in tongue squamous cell carcinoma.BMC cancer · 2016Article
- Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Prostaglandin E2 that triggers fever is synthesized through an endocannabinoid- dependent pathway.Temperature (Austin, Tex.)Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fever is a common response to inflammation and infection. The mechanism involves prostaglandin E2 (PGE2)-EP3 receptor signaling in the hypothalamus, which raises the set point of hypothalamic thermostat for body temperature, but the lipid metabolic pathway for pyretic PGE2 production remains unknown. To reveal the molecular basis of fever initiation, we examined lipopolysaccharides (LPS)-induced fever model in monoacylglycerol lipase (MGL)-deficient (Mgll-/-) mice, CB1 receptor-MGL compound-deficient (Cnr1-/-Mgll-/-) mice, cytosolic phospholipase A2α (cPLA2α)-deficient (Pla2g4a-/-) mice, and diacylglycerol lipase α (DGLα)-deficient (Dagla-/-) mice. Febrile reactions were abolished in Mgll-/- and Cnr1-/-Mgll-/- mice, whereas Cnr1-/-Mgll+/+, Pla2g4a-/- and Dagla-/- mice responded normally, demonstrating that MGL is a critical enzyme for fever, which functions independently of endocannabinoid signals. Intracerebroventricular administration of PGE2 caused fever similarly in Mgll-/- and wild-type control mice, suggesting a lack of pyretic PGE2 production in Mgll-/- hypothalamus, which was confirmed by lipidomics analysis. Normal blood cytokine responses after LPS administration suggested that MGL-deficiency does not affect pyretic cytokine productions. Diurnal body temperature profiles were normal in Mgll-/- mice, demonstrating that MGL is unrelated to physiological thermoregulation. In conclusion, MGL-dependent hydrolysis of endocannabinoid 2-arachidonoylglycerol is necessary for pyretic PGE2 production in the hypothalamus.
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