RESUMO
BACKGROUND: Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) recommendations are frequently stated at 500 mg/d; however, adherence to these recommendations would result in a large global commercial EPA/DHA production deficit. Previously, our laboratory demonstrated that acute DHA intake in rats can increase the capacity for synthesis-secretion of n-3 (ω-3) polyunsaturated fatty acids (PUFAs). OBJECTIVE: We aimed to investigate the utility of a dietary DHA cycling strategy that employs 2 wk of repeated DHA feeding for a total of 3 cycles over 12 wk. METHODS: Male Long-Evans rats were fed a 10% fat diet by weight comprised of either 1) a 2-wk, 2% α-linolenic acid (ALA, DHA-ALA group 18:3n-3) diet followed by a 2-wk, 2% DHA + 2% ALA diet over 3 consecutive 4-wk periods ("DHA cycling," DHA-ALA group); 2) a 2% DHA + 2% ALA diet (DHA group) for 12 wk; or 3) a 2% ALA-only diet (ALA group) for 12 wk. At 15 wk old, blood and tissue fatty acid concentrations and liver mRNA expression and 13C-DHA natural abundances were determined. RESULTS: DHA concentrations in plasma, erythrocytes, and whole blood between the DHA-ALA group and the DHA groups were not different (P ≥ 0.05), but were 72-110% higher (P < 0.05) than in the ALA group. Similarly, DHA concentrations in liver, heart, adipose, and brain were not different (P ≥ 0.05) between the DHA-fed groups, but were at least 62%, 72%, 320%, and 68% higher (P < 0.05) than in the ALA group in liver, heart, adipose, and skeletal muscle, respectively. Compound-specific isotope analysis indicated that 310% more liver DHA in the DHA-ALA group compared with the DHA group is derived from dietary ALA, and this was accompanied by a 123% and 93% higher expression of elongation of very long-chain (Elovl)2 and Elovl5, respectively, in the DHA-ALA group compared with the ALA group. CONCLUSIONS: DHA cycling requires half the dietary DHA while achieving equal blood and tissue DHA concentrations in rats. Implementation of such dietary strategies in humans could reduce the gap between global dietary n-3 PUFA recommendations and commercial production.
Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Ácido alfa-Linolênico/metabolismo , Tecido Adiposo/química , Animais , Química Encefálica , Ácidos Docosa-Hexaenoicos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Eritrócitos , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Vacina contra Caxumba/química , Músculo Esquelético/química , Miocárdio/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Long-EvansRESUMO
OBJECTIVES: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer's disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear. METHODS: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-ß 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques. RESULTS: GFAP increased in all groups in response to amyloid-ß, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-ß infusion than wildtype safflower animals. CONCLUSION: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-ß 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-ß than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.
Assuntos
Peptídeos beta-Amiloides/administração & dosagem , Astrócitos/metabolismo , Proteínas de Caenorhabditis elegans/genética , Encefalite/metabolismo , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Ômega-3/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Animais , Astrócitos/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Infusões Intraventriculares , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Óleo de Cártamo/administração & dosagem , TransgenesRESUMO
Young adult females have higher blood docosahexaenoic acid (DHA), 22:6n-3 levels than males, and this is believed to be due to higher DHA synthesis rates, although DHA may also accumulate due to a longer half-life or a combination of both. However, sex differences in blood fatty acid responses to eicosapentaenoic acid (EPA), 20:5n-3 or DHA supplementation have not been fully investigated. In this exploratory analysis, females and males (n = 14-15 per group) were supplemented with 3 g/day EPA, 3 g/day DHA, or olive oil control for 12 weeks. Plasma was analyzed for sex effects at baseline and changes following 12 weeks' supplementation for fatty acid levels and carbon-13 signature (δ13 C). Following EPA supplementation, the increase in plasma DHA in females (+23.8 ± 11.8, nmol/mL ± SEM) was higher than males (-13.8 ± 9.2, p < 0.01). The increase in plasma δ13 C-DHA of females (+2.79 ± 0.31, milliUrey (mUr ± SEM) compared with males (+1.88 ± 0.44) did not reach statistical significance (p = 0.10). The sex effect appears driven largely by increased plasma DHA in the AA genotype of females (+58.8 ± 11.5, nmol/mL ± SEM, n = 5) compared to GA + GG in females (+4.34 ± 13.5, n = 9) and AA in males (-29.1 ± 17.2, n = 6) for rs953413 in the ELOVL2 gene (p < 0.001). In conclusion, EPA supplementation increases plasma DHA levels in females compared to males, which may be dependent on the AA genotype for rs953413 in ELOVL2.
Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/análogos & derivados , Elongases de Ácidos Graxos/genética , Polimorfismo de Nucleotídeo Único/genética , Suplementos Nutricionais , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/farmacologia , Elongases de Ácidos Graxos/sangue , Feminino , Genótipo , Humanos , MasculinoRESUMO
BACKGROUND: It has long been believed that DHA supplementation increases plasma EPA via the retroconversion pathway in mammals. However, in rodents this increase in EPA is likely due to a slower metabolism of EPA, but this has never been tested directly in humans. OBJECTIVE: The aim of this study was to use the natural variations in 13C:12C ratio (carbon-13 isotopic abundance [δ13C]) of n-3 PUFA supplements to assess n-3 PUFA metabolism following DHA or EPA supplementation in humans. METHODS: Participants (aged 21.6 ± 2.2 y) were randomly assigned into 1 of 3 supplement groups for 12 wk: 1) olive oil control, 2) â¼3 g/d DHA, or 3) â¼3 g/d EPA. Blood was collected before and after the supplementation period, and concentrations and δ13C of plasma n-3 PUFA were determined. RESULTS: DHA supplementation increased (P < 0.05) plasma EPA concentrations by 130% but did not affect plasma δ13C-EPA (-31.0 ± 0.30 to -30.8 ± 0.19, milliUrey ± SEM, P > 0.05). In addition, EPA supplementation did not change plasma DHA concentrations (P > 0.05) but did increase plasma δ13C-DHA (-27.9 ± 0.2 to -25.6 ± 0.1, P < 0.05) toward δ13C-EPA of the supplement (-23.5 ± 0.22). EPA supplementation increased plasma concentrations of EPA and docosapentaenoic acid (DPAn-3) by 880% and 200%, respectively, and increased plasma δ13C-EPA (-31.5 ± 0.2 to -25.7 ± 0.2) and δ13C-DPAn-3 (-28.9 ± 0.3 to -25.0 ± 0.1) toward δ13C-EPA of the supplement. CONCLUSIONS: In this study, we show that the increase in plasma EPA following DHA supplementation in humans does not occur via retroconversion, but instead from a slowed metabolism and/or accumulation of plasma EPA. Furthermore, substantial amounts of supplemental EPA can be converted into DHA. δ13C of n-3 PUFA in humans is a powerful and underutilized tool that can track dietary n-3 PUFA and elucidate complex metabolic questions. This trial was registered at clinicaltrials.gov as NCT03378232.
Assuntos
Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/metabolismo , Isótopos de Carbono , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/química , Método Duplo-Cego , Ácido Eicosapentaenoico/química , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Comparative studies suggest that DHA may have stronger serum triglyceride-lowering effects than EPA; however, the molecular basis for this differential effect remains unexplored in humans. Differential regulation of lipogenesis and triglyceride clearance are 2 possible mechanisms of action. OBJECTIVES: We compared the effects of EPA and DHA supplementation on serum triglycerides, markers of lipogenesis, and lipoprotein lipase (LPL) activity in adults participating in a double-blind, multiarm, placebo-controlled parallel-group randomized trial. Lipogenesis was assessed with the lipogenic index and compound specific isotope analysis (CSIA). METHODS: Young, healthy normolipidemic men and women (n = 89; 21.6 ± 0.23 y; mean ± SEM) were randomly allocated into 1 of 3 supplement groups for 12 wk: 1) olive oil, 2) â¼3 g EPA/d, and 3) â¼3 g DHA/d. Omega-3 supplements were provided in triglyceride form. Blood was collected before and after supplementation for the analysis of fatty acids and preheparin LPL activity. Variations in the 13C:12C ratio (δ13C) of palmitate (16:0) and linoleate (18:2n-6) were measured by CSIA. RESULTS: DHA supplementation reduced blood triglycerides (0.85 ± 0.04 mmol/L to 0.65 ± 0.03 mmol/L; P < 0.01), with no change seen with EPA supplementation. DHA supplementation did not change the lipogenic index or δ13C-16:0, whereas EPA supplementation increased the lipogenic index by 11% (P < 0.01) and δ13C-16:0 (P = 0.03) from -23.2 ± 0.2 to -22.8 ± 0.2 milliUrey ± SEM. CONCLUSIONS: Reduced triglyceride concentrations after DHA supplementation are associated with increased LPL activity, whereas the null effect of EPA supplementation on blood triglycerides may stem from the concomitant increases in lipogenesis and LPL activity. Further investigation of the differential triglyceride-lowering effects of EPA and DHA is warranted in both normolipidemic and hyperlipidemic individuals. This trial was registered at clinicaltrials.gov as NCT03378232.