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Molecules (Basel, Switzerland) Oct 2020Omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and vitamin D are essential components of human nutrition. A regular human diet is highly deficient in n-3...
Nutritional Enhancement of Farmed Salmon Meat via Non-GMO Nannochloropsis Gaditana: Eicosapentaenoic Acid (EPA, 20:5 n-3), Docosapentaenoic Acid (DPA, 22:5 n-3) and Vitamin D3 for Human Health.
Omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and vitamin D are essential components of human nutrition. A regular human diet is highly deficient in n-3 LC PUFAs. Fish like salmon are highly recommended in the human diet as they are a major source of high-value n-3 LC PUFAs and vitamin D The levels of these nutrients have been decreasing over the last few years in farmed salmon, whose production urgently needs sustainable sources of these nutrients. The microalga (NG) is known for its naturally high potential for the production of eicosapentaenoic (EPA, 20:5 n-3) fatty acid. A commercial diet for Atlantic salmon was supplemented with 1% and 10% of spray-dried NG grown under controlled conditions for a high EPA content. Salmon were harvested on day 49, following which, boneless and skinless salmon meat was recovered from fish and analyzed for the fatty acid profile, total fat, and vitamin D. Vitamin D, EPA, and docosapentaenoic fatty acid (DPA, 22:5 n-3) levels were significantly increased ( < 0.05) by supplementing the basal diet with 10% NG, thus, NG represents a novel, functional, natural ingredient and a sustainable source of n-3 LC-PUFAs that can raise the levels of healthy fats and vitamin D in farmed salmon meat.
Topics: Animals; Cholecalciferol; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans; Microalgae; Salmo salar
PubMed: 33050537
DOI: 10.3390/molecules25204615 -
Clinical Epigenetics Feb 2024Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS).
RESULTS
DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10, 95%CI: 1.28 × 10-2.73 × 10, P value: 6.98 × 10), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10, 95%CI: 6.25 × 10-1.33 × 10, P value: 6.75 × 10). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10, 95% CI: 1.27 × 10-2.73 × 10, P value = 5.99 × 10) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10, 95% CI: 1.31 × 10-2.83 × 10, P value = 1.00 × 10 and beta: 2.19 × 10, 95% CI: 1.41 × 10-2.97 × 10, P value = 5.91 × 10 respectively).
CONCLUSIONS
Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.
Topics: Humans; Epigenome; DNA Methylation; Fatty Acids, Omega-3; Fatty Acids; Docosahexaenoic Acids; Repressor Proteins
PubMed: 38365790
DOI: 10.1186/s13148-024-01643-9 -
Nutrients Jan 2022The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated...
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Diet; Dietary Fats; Docosahexaenoic Acids; Female; Guinea Pigs; Linoleic Acid; Maternal Nutritional Physiological Phenomena; Phospholipids; Pregnancy; Retina; alpha-Linolenic Acid
PubMed: 35057481
DOI: 10.3390/nu14020301 -
Ecotoxicology and Environmental Safety Mar 202211 S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid (DoPE) is a derivative of docosapentaenoic acid, a specialized pro-resolving mediator of inflammation...
The DPA-derivative 11S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM.
11 S, 17S-dihydroxy 7,9,13,15,19 (Z,E,Z,E,Z)-docosapentaenoic acid (DoPE) is a derivative of docosapentaenoic acid, a specialized pro-resolving mediator of inflammation such as lipoxins, resolvins, maresins, and protectins. PM is a fine dust particle that induces oxidative stress, DNA damage, inflammation, aging, and cancer. The anti-inflammatory mechanism of DoPE, however, has not yet been elucidated. In these studies, we investigated whether DoPE has anti-inflammatory effects in human keratinocyte HaCaT cells. We demonstrated that DoPE suppressed PM-induced expressions of IL-6 mRNA and protein in human HaCaT keratinocytes. We also investigated the modulating effects of DoPE on reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK). ROS production, extracellular signal regulated kinase (ERK) phosphorylation, and translocation of nuclear factor-kappa B (NF-kB) p65 and NF-kB activity were suppressed by DoPE in PM-stimulated HaCaT cells. Collectively, our results demonstrated that DoPE inhibited IL-6 expression by reducing ROS generation, suppressing ERK phosphorylation, and inhibiting translocation of NF-kB p65 and NF-kB activity in PM-stimulated HaCaT cells, suggesting that DoPE can be useful for the resolution of the inflammation caused by IL-6.
Topics: Dust; Extracellular Signal-Regulated MAP Kinases; Fatty Acids, Unsaturated; Humans; Interleukin-6; Keratinocytes; NF-kappa B; Reactive Oxygen Species
PubMed: 35104780
DOI: 10.1016/j.ecoenv.2022.113252 -
The Journal of Biological Chemistry Jan 2023Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the...
Astrocytic excitatory amino acid transporter 2 (EAAT2) plays a major role in removing the excitatory neurotransmitter L-glutamate (L-Glu) from synaptic clefts in the forebrain to prevent excitotoxicity. Polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6 n-3) enhance synaptic transmission, and their target molecules include EAATs. Here, we aimed to investigate the effect of DHA on EAAT2 and identify the key amino acid for DHA/EAAT2 interaction by electrophysiological recording of L-Glu-induced current in Xenopus oocytes transfected with EAATs, their chimeras, and single mutants. DHA transiently increased the amplitude of EAAT2 but tended to decrease that of excitatory amino acid transporter subtype 1 (EAAT1), another astrocytic EAAT. Single mutation of leucine (Leu) 434 to alanine (Ala) completely suppressed the augmentation by DHA, while mutation of EAAT1 Ala 435 (corresponding to EAAT2 Leu434) to Leu changed the effect from suppression to augmentation. Other polyunsaturated fatty acids (docosapentaenoic acid, eicosapentaenoic acid, arachidonic acid, and α-linolenic acid) similarly augmented the EAAT2 current and suppressed the EAAT1 current. Finally, our docking analysis suggested the most stable docking site is the lipid crevice of EAAT2, in close proximity to the L-Glu and sodium binding sites, suggesting that the DHA/Leu434 interaction might affect the elevator-like slide and/or the shapes of the other binding sites. Collectively, our results highlight a key molecular detail in the DHA-induced regulation of synaptic transmission involving EAATs.
Topics: Docosahexaenoic Acids; Excitatory Amino Acid Transporter 2; Glutamic Acid; Leucine; Synaptic Transmission; Mutation; Xenopus laevis
PubMed: 36509140
DOI: 10.1016/j.jbc.2022.102793 -
Biological & Pharmaceutical Bulletin 2021Long-chain acyl-CoA synthetases (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their active form, acyl-CoAs. Recent knock-out mouse...
Long-chain acyl-CoA synthetases (ACSLs) are a family of enzymes that convert long-chain free fatty acids into their active form, acyl-CoAs. Recent knock-out mouse studies revealed that among ACSL isoenzymes, ACSL6 plays an important role in the maintenance of docosahexaenoic acid (DHA)-containing glycerophospholipids. Several transcript variants of the human ACSL6 gene have been found; the two major ACSL6 variants, ACSL6V1 and V2, encode slightly different short motifs that both contain a conserved structural domain, the fatty acid Gate domain. In the present study, we expressed recombinant human ACSL6V1 and V2 in Spodoptera frugiperda 9 (Sf9) cells using the baculovirus expression system, and then, using our novel ACSL assay system with liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined the substrate specificities of the recombinant human ACSL6V1 and V2 proteins. The results showed that both ACSL6V1 and V2 could convert various kinds of long-chain fatty acids into their acyl-CoAs. Oleic acid was a good common substrate and eicosapolyenoic acids were poor common substrates for both variants. However, ACSL6V1 and V2 differed considerably in their preferences for octadecapolyenoic acids, such as linoleic acid, and docosapolyenoic acids, such as DHA and docosapentaenoic acid (DPA): ACSL6V1 preferred octadecapolyenoic acids, whereas V2 strongly preferred docosapolyenoic acids. Moreover, our kinetic studies revealed that ACSL6V2 had a much higher affinity for DHA than ACSL6V1. Our results suggested that ACSL6V1 and V2 might exert different physiological functions and indicated that ACSL6V2 might be critical for the maintenance of membrane phospholipids bearing docosapolyenoic acids such as DHA.
Topics: Animals; Coenzyme A Ligases; Docosahexaenoic Acids; Enzyme Assays; Humans; Isoenzymes; Kinetics; Linoleic Acid; Phospholipids; Recombinant Proteins; Sf9 Cells; Spodoptera; Stearic Acids; Substrate Specificity; Tandem Mass Spectrometry
PubMed: 34602568
DOI: 10.1248/bpb.b21-00551 -
Frontiers in Nutrition 2024Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma...
BACKGROUND
Depression is associated with greater functional impairment and high societal costs than many other mental disorders. Research on the association between plasma polyunsaturated fatty acids (PUFAs) levels and depression have yielded inconsistent results.
OBJECTIVE
To evaluate whether plasma n-3 and n-6 PUFAs levels are associated with depression in American adults.
METHODS
A cross-sectional study included 2053 adults (aged ≥20 y) in the National Health and Nutrition Examination Survey (NHANES), 2011-2012. The level of plasma n-3 and n-6 PUFAs were obtained for analysis. Self-reported Patient Health Questionnaire-9 (PHQ-9) was used to identify the depression status. Binary logistic regression analysis was performed to evaluate the association between quartiles of plasma n-3 and n-6 PUFAs and depression after adjustments for confounders.
RESULTS
The study of 2053 respondents over 20 years of age with a weighted depression prevalence of 7.29% comprised 1,043 men (weighted proportion, 49.13%) and 1,010 women (weighted, 50.87%), with a weighted mean (SE) age of 47.58 (0.67) years. Significantly increased risks of depression over non-depression were observed in the third quartiles (OR = 1.65, 95% CI = 1.05-2.62) for arachidonic acid (AA; 20:4n-6); the third quartiles (OR = 2.20, 95% CI = 1.20-4.05) for docosatetraenoic acid (DTA; 22:4n-6); the third (OR = 2.33, 95% CI = 1.34-4.07), and highest quartiles (OR = 1.83, 95% CI = 1.03-3.26) for docosapentaenoic acid (DPAn-6; 22:5n-6); and the third (OR = 2.18, 95% CI = 1.18-4.03) and highest quartiles (OR = 2.47, 95% CI = 1.31-4.68) for docosapentaenoic acid (DPAn-3; 22:5n-3); the second (OR = 2.13, 95% CI = 1.24-3.66), third (OR = 2.40, 95% CI = 1.28-4.50), and highest quartiles (OR = 2.24, 95% CI = 1.08-4.69) for AA/docosahexaenoic acid (DHA; 22:6n-3) ratio compared with the lowest quartile after adjusting for confounding factors.
CONCLUSION
Higher plasma levels of AA, DTA, DPAn-6, DPAn-3 PUFAs, and AA/DHA ratio may be potential risk factors for depression in US adults.
PubMed: 38544754
DOI: 10.3389/fnut.2024.1342304 -
Frontiers in Nutrition 2023In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported...
BACKGROUND
In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets.
METHODS
Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), -docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records.
RESULTS
Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: = <0.05, fatty acids: = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period ( = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods.
CONCLUSION
This study indicates that the participants in the ADIRA trial were compliant to the study diets regarding intake of whole grain, cooking fat, seafood, and red meat, and the intended overall dietary fat quality. Compliance to instructions on fruit- and vegetable intake remains uncertain.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1, NCT02941055.
PubMed: 37426179
DOI: 10.3389/fnut.2023.1209787 -
Journal of Atherosclerosis and... Aug 2023To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii,...
AIM
To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.
METHODS
Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis.
RESULTS
Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.
CONCLUSIONS
Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.
Topics: Animals; Female; Humans; Male; Asian; Fatty Acids, Omega-3; Lipoproteins, HDL; Lipoproteins, LDL; Smoking; Adult; Middle Aged; Hawaii; East Asian People; Japan; Health Status
PubMed: 36328528
DOI: 10.5551/jat.63762 -
Marine Drugs Jan 2023Although the tumor bulk is initially reduced by 5-fluorouracil (5-FU), chemoresistance developed due to prolonged chemotherapy in colorectal cancer (CRC). The enrichment...
7,15-Dihydroxy-16,17-epoxy-docosapentaenoic Acid Overcomes Chemoresistance of 5-Fluorouracil by Suppressing the Infiltration of Tumor-Associated Macrophages and Inhibiting the Activation of Cancer Stem Cells in a Colorectal Cancer Xenograft Model.
Although the tumor bulk is initially reduced by 5-fluorouracil (5-FU), chemoresistance developed due to prolonged chemotherapy in colorectal cancer (CRC). The enrichment of cancer stem cells (CSCs) and the infiltration of tumor-associated macrophages (TAMs) contribute to chemoresistance and poor outcomes. A docosahexaenoic acid derivative developed by our group, 7,15-dihydroxy-16,17-epoxy-docosapentaenoic acid (diHEP-DPA), exerts antitumor effects against TAMs infiltration and CSCs enrichment in our previous study. The current study aimed to investigate whether diHEP-DPA was able to overcome chemoresistance to 5-FU in CRCs, together with the potential synergistic mechanisms in a CT26-BALB/c mouse model. Our results suggested that although 5-FU inhibited tumor growth, 5-FU enriched CSCs via the WNT/β-catenin signaling pathway, resulting in chemoresistance in CRCs. However, we revealed that 5-FU promoted the infiltration of TAMs via the NF-kB signaling pathway and improved epithelial-mesenchymal transition (EMT) via the signal transducer and activator of the transcription 3 (STAT3) signaling pathway; these traits were believed to contribute to CSC activation. Furthermore, supplementation with diHEP-DPA could overcome drug resistance by decreasing the CSCs, suppressing the infiltration of TAMs, and inhibiting EMT progression. Additionally, the combinatorial treatment of diHEP-DPA and 5-FU effectively enhanced phagocytosis by blocking the CD47/signal regulatory protein alpha (SIRPα) axis. These findings present that diHEP-DPA is a potential therapeutic supplement to improve drug outcomes and suppress chemoresistance associated with the current 5-FU-based therapies for colorectal cancer.
Topics: Mice; Animals; Humans; Fluorouracil; Drug Resistance, Neoplasm; Tumor-Associated Macrophages; Heterografts; Cell Line, Tumor; Colorectal Neoplasms; Wnt Signaling Pathway; Neoplastic Stem Cells
PubMed: 36827121
DOI: 10.3390/md21020080