Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis
Borsini A, Nicolaou A, Camacho-Muñoz D, Kendall AC, Di Benedetto MG, Giacobbe J, Su KP, Pariante CM
Molecular psychiatry · 180 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
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- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- South London and Maudsley NHS Foundation Trust
- Organización sin fines de lucro
- Wellcome Trust
- Gobierno
- National Institute for Health and Care Research
- Universidad u hospital
- King's College London
- Gobierno
- European Commission
- Organización sin fines de lucro
- Rosetrees Trust
- Universidad u hospital
- China Medical University Hospital
- Gobierno
- Ministry of Science and Technology, Taiwan
- Universidad u hospital
- China Medical University
- Universidad u hospital
- Tainan Municipal An-Nan Hospital
- Universidad u hospital
- Manchester Biomedical Research Centre
- Gobierno
- Medical Research Council
- Gobierno
- Division of Materials Research
- Gobierno
- National Institute for Health Research (NIHR)
- Organización sin fines de lucro
- Rosetrees
- Subvenciones
- China Medical University (109-2320-B-038-057-MY3); China Medical University Hospital (DMR‐109‐102); China Medical University (DMR-109-102); China Medical University Hospital (DMR-HHC-109-11); Wellcome Trust (WT094028/B); China Medical University Hospital (109‐102); Ministry of Science and Technology, Taiwan (MOST109-2320-B039-066); China Medical University Hospital (CMU104-S-16-01); China Medical University Hospital (DMR‐109‐244); China Medical University (109-102); Ministry of Science and Technology, Taiwan (2314-B-039); South London and Maudsley NHS Foundation Trust (MR/L014815/1); Medical Research Council (MR/N029488/1); Medical Research Council (MR/L014815/1); China Medical University Hospital (CRS-108-048); National Institute for Health and Care Research (MR/J002739/1); China Medical University Hospital (CMU103‐BC‐4‐1); European Commission (SC1-BHC); China Medical University Hospital (DMR-108-216); Tainan Municipal An-Nan Hospital (ANHRF109-31); China Medical University (DMR‐HHC‐109‐11); National Institute for Health and Care Research (MR/L014815/1); China Medical University Hospital (109‐244); Ministry of Science and Technology, Taiwan (2320-B-039); European Commission (SC1-BHC-01-2019); China Medical University (CMU108‐SR‐106); South London and Maudsley NHS Foundation Trust (MR/J002739/1); European Commission (HORIZON2020); China Medical University (CRS-108-048); National Institute for Health and Care Research (NIHR201376); Ministry of Science and Technology, Taiwan (CMRC CMA-3); Wellcome Trust (WT094028); National Institute for Health and Care Research (NF-SI-0616-10074); China Medical University (CMU104-S-16-01); Medical Research Council (MR/N029488/1); China Medical University (109-244); China Medical University (DMR‐108‐216); Medical Research Council (MR/J002739/1); Ministry of Science and Technology, Taiwan (ANHRF109-31); Ministry of Science and Technology, Taiwan (CMU108-SR-106); China Medical University (DMR‐109‐244); Ministry of Science and Technology, Taiwan (MOST 108-); China Medical University (CMU103-BC-4-1); Ministry of Science and Technology, Taiwan (DMR-108); China Medical University Hospital (109-2320-B-038-057-MY3); Ministry of Science and Technology, Taiwan (MOST108-2314-B039-016); Ministry of Science and Technology, Taiwan (MOST109-2320-B038-057-MY3); Wellcome Trust (WT094028/AIA); Ministry of Science and Technology, Taiwan (DMR-109); Medical Research Council (MR/J002739/1); Medical Research Council (MR/L014815/1)
Según 15 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2021-06-15 · Mol Psychiatry · vol. 26 · número 11 · págs. 6773–6788
- Editorial
- Springer Nature
- Citado
- 234 citas · más que el 100% de estudios similares · 16.5× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 64 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Fatty Acid Research and Health · Tryptophan and brain disorders · Eicosanoids and Hypertension Pharmacology
- Palabras clave
- omega-3 polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, major depressive disorder, hippocampal neurogenesis, inflammation, lipoxygenase metabolites, cytochrome P450 metabolites, soluble epoxide hydrolase, anti-inflammatory activity, antidepressant effects, neuroprotection, apoptosis, cytokines, dietary supplementation, lipidomics
- MeSH
- hippocampus, humans, inflammation, cytochrome p-450 enzyme system, lipoxygenase, fatty acids, omega-3, docosahexaenoic acids, eicosapentaenoic acid, depression, neurogenesis, major depressive disorder
8 autores
- Alessandra Borsini🇬🇧 · autor de correspondenciaKing's College London
- Anna Nicolaou🇬🇧University of Manchester
- Dolores Camacho‐Muñoz🇬🇧University of Manchester
- Alexandra C. Kendall🇬🇧University of Manchester
- Maria Grazia Di Benedetto🇬🇧🇮🇹King's College London; Centro San Giovanni di Dio Fatebenefratelli
- Juliette Giacobbe🇬🇧King's College London
- Kuan‐Pin Su🇬🇧🇹🇼 · autor de correspondenciaKing's College London; China Medical University; An-Nan Hospital
- Carmine Maria Pariante🇬🇧King's College London
Resumen
El texto original del estudio, en el idioma en que se publicó.
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can exert antidepressant, anti-inflammatory and neuroprotective properties, but the exact molecular mechanism underlying their effects is still not fully understood. We conducted both in vitro and clinical investigations to test which EPA or DHA metabolites are involved in these anti-inflammatory, neuroprotective and antidepressant effects. In vitro, we used the human hippocampal progenitor cell line HPC0A07/03C, and pre-treated cells with either EPA or DHA, followed by interleukin 1beta (IL1β), IL6 and interferon-alpha (IFN-α). Both EPA and DHA prevented the reduction in neurogenesis and the increase in apoptosis induced by these cytokines; moreover, these effects were mediated by the lipoxygenase (LOX) and cytochrome P450 (CYP450) EPA/DHA metabolites, 5-hydroxyeicosapentaenoic acid (HEPE), 4-hydroxydocosahexaenoic acid (HDHA), 18-HEPE, 20-HDHA, 17(18)-epoxyeicosatetraenoic acid (EpETE) and 19(20)-epoxydocosapentaenoic acid (EpDPA), detected here for the first time in human hippocampal neurones using mass spectrometry lipidomics of the supernatant. In fact, like EPA/DHA, co-treatment with these metabolites prevented cytokines-induced reduction in neurogenesis and apoptosis. Moreover, co-treatment with 17(18)-EpETE and 19(20)-EpDPA and the soluble epoxide hydroxylase (sEH) inhibitor, TPPU (which prevents their conversion into dihydroxyeicosatetraenoic acid (DiHETE)/ dihydroxydocosapentaenoic acid (DiHDPA) metabolites) further enhanced their neurogenic and anti-apoptotic effects. Interestingly, these findings were replicated in a sample of n = 22 patients with a DSM-IV Major Depressive Disorder, randomly assigned to treatment with either EPA (3.0 g/day) or DHA (1.4 g/day) for 12 weeks, with exactly the same LOX and CYP450 lipid metabolites increased in the plasma of these patients following treatment with their precursor, EPA or DHA, and some evidence that higher levels of these metabolites were correlated with less severe depressive symptoms. Overall, our study provides the first evidence for the relevance of LOX- and CYP450-derived EPA/DHA bioactive lipid metabolites as neuroprotective molecular targets for human hippocampal neurogenesis and depression, and highlights the importance of sEH inhibitors as potential therapeutic strategy for patients suffering from depressive symptoms.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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