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Nutrition ; 123: 112413, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38518540


OBJECTIVES: We assessed the joint effects of omega (n)-3 fatty acid supplementation and dietary fish intake on systemic lipid mediators of inflammation among adults. METHODS: Within VITAL, a double-blind randomized controlled trial, adults were randomized to ω-3 fatty acids (460 mg EPA + 380 mg DHA/d) or placebo. We selected participants who reported low (<1 serving/mo) baseline dietary fish intake and matched them by age, sex, race, and trial arm to participants with self-reported highest fish intake (≥3.9 servings/wk). Baseline and 1-y plasma samples were tested for 9 ω-3 fatty acid-derived lipid mediators. Multivariable linear models assessed lipid mediator changes and joint effects of ω-3 fatty acid supplementation and dietary fish intake. RESULTS: Forty-eight participants with low baseline fish intake were matched to 48 with high fish intake. Mean age was 64.6 (±7.26), 50% were female, and 85% non-Hispanic white. One-year lipid mediator changes in expected directions were observed in those receiving ω-3 fatty acids versus placebo: reductions in proinflammatory mediators, PGD2, 5-HETE, and 12-HETE; increases in proresolving mediators, EPA and DHA. Larger 1-y lipid biomarker changes were seen in those with low baseline fish intake randomized to active ω-3 fatty acids for DHA, EPA, PGD2, Resolvin D1, and Resolvin D4 were observed, although no significant multiplicative interactions were detected. DISCUSSION: Beneficial changes in circulating proresolving and proinflammatory mediators were found with 1-y of ω-3 fatty acid supplementation versus placebo for all participants, with a trend toward larger effects among those with low baseline fish intake, although interactions were not significant.

Suplementos Dietéticos , Ácidos Docosahexaenoicos , Ácidos Grasos Omega-3 , Peces , Inflamación , Alimentos Marinos , Humanos , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Inflamación/sangre , Animales , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Anciano , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Ácido Eicosapentaenoico/administración & dosificación , Dieta/métodos
Proc Natl Acad Sci U S A ; 113(43): 12232-12237, 2016 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-27791009


Macrophages are central in coordinating immune responses, tissue repair, and regeneration, with different subtypes being associated with inflammation-initiating and proresolving actions. We recently identified a family of macrophage-derived proresolving and tissue regenerative molecules coined maresin conjugates in tissue regeneration (MCTR). Herein, using lipid mediator profiling we identified MCTR in human serum, lymph nodes, and plasma and investigated MCTR biosynthetic pathways in human macrophages. With human recombinant enzymes, primary cells, and enantiomerically pure compounds we found that the synthetic maresin epoxide intermediate 13S,14S-eMaR (13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid) was converted to MCTR1 (13R-glutathionyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) by LTC4S and GSTM4. Incubation of human macrophages with LTC4S inhibitors blocked LTC4 and increased resolvins and lipoxins. The conversion of MCTR1 to MCTR2 (13R-cysteinylglycinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid) was catalyzed by γ-glutamyl transferase (GGT) in human macrophages. Biosynthesis of MCTR3 was mediated by dipeptidases that cleaved the cysteinyl-glycinyl bond of MCTR2 to give 13R-cysteinyl, 14S-hydroxy-4Z,7Z,9E,11E,13R,14S,16Z,19Z-docosahexaenoic acid. Of note, both GSTM4 and GGT enzymes displayed higher affinity to 13S,14S-eMaR and MCTR1 compared with their classic substrates in the cysteinyl leukotriene metabolome. Together these results establish the MCTR biosynthetic pathway and provide mechanisms in tissue repair and regeneration.

Ácidos Docosahexaenoicos/metabolismo , Inflamación/metabolismo , Lípidos/genética , Regeneración/genética , Vías Biosintéticas/genética , Ácidos Docosahexaenoicos/genética , Compuestos Epoxi/química , Compuestos Epoxi/metabolismo , Humanos , Inflamación/genética , Metabolismo de los Lípidos/genética , Lípidos/sangre , Ganglios Linfáticos/crecimiento & desarrollo , Ganglios Linfáticos/metabolismo , Macrófagos/metabolismo , Estructura Molecular , Estereoisomerismo , Cicatrización de Heridas/genética