Plasma oxylipin profile discriminates ethnicities in subjects with Non-alcoholic steatohepatitis: An exploratory analysis

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver pathologies from steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). With no clear mechanism, it affects Hispanics in the U.S. disproportionately compared to other ethnicities. Polyunsaturated fatty acids (PUFAs) metabolism and downstream inflammatory lipid mediators including oxylipin (OXL) and endocannabinoid (eCB) are altered in NAFLD and thought to contribute to its pathogenesis. It is not clear if variations in PUFA metabolism and downstream lipid mediators characterize ethnicity in NAFLD. This pilot study employed targeted lipidomic profiling for plasma PUFAs, non-esterified OXLs and eCBs in White Hispanics (HIS, n =10) and Caucasians (CAU, n =8) with obesity and biopsy-confirmed NAFL, compared with healthy control subjects (HC; n =14 HIS; n =8 CAU). Results indicate diminished long chain PUFA profile in HIS with NAFL and NASH, independent of obesity and histological severity. The profiling data also detected differences in plasma OXLs and eCBs profiles by ethnicity group in NASH, including lower levels of arachidonic acid derived OXLs observed in HIS. We conducted a secondary analysis to compare ethnicities within NASH (n =12 HIS; n =17 CAU). Results showed that plasma OXL profiles distinguished ethnicities with NASH and confirmed ethnicity-related differences in arachidonic acid metabolism. Our data also suggest lower lipoxygenase(s) and higher soluble epoxide hydrolase(s) activities in HIS compared to CAU with NASH. The underlying causes and implications of these differences on NAFLD severity are not clear and worth further investigation. Our findings provide preliminary data suggesting ethnicity-specific plasma lipidomic signature characterizing NASH that requires validation.

DNA Damage, n-3 Long-Chain PUFA Levels and Proteomic Profile in Brazilian Children and Adolescents

Fatty acids play a significant role in maintaining cellular and DNA protection and we previously found an inverse relationship between blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and DNA damage. The aim of this study was to explore differences in proteomic profiles, for 117 pro-inflammatory proteins, in two previously defined groups of individuals with different DNA damage and EPA and DHA levels. Healthy children and adolescents (n = 140) aged 9 to 13 years old in an urban area of Brazil were divided by k-means cluster test into two clusters of DNA damage (tail intensity) using the comet assay (cluster 1 = 5.9% ± 1.2 and cluster 2 = 13.8% ± 3.1) in our previous study. The cluster with higher DNA damage and lower levels of DHA (6.2 ± 1.6 mg/dL; 5.4 ± 1.3 mg/dL, p = 0.003) and EPA (0.6 ± 0.2 mg/dL; 0.5 ± 0.1 mg/dL, p < 0.001) presented increased expression of the proteins CDK8–CCNC, PIK3CA–PIK3R1, KYNU, and PRKCB, which are involved in pro-inflammatory pathways. Our findings support the hypothesis that low levels of n-3 long-chain PUFA may have a less protective role against DNA damage through expression of pro-inflammatory proteins, such as CDK8–CCNC, PIK3CA–PIK3R1, KYNU, and PRKCB.

Effects of longissimus muscle fatty acid composition in mongolian sheep breeds

This survey to comparative investigates on fat and fatty acid composition in muscles depends on season effects of pastoral and grain fed Mongolian breeds sheep (Mongolian grassland pastoral Mongolian sheep, Inner Mongolian grassland pastoral and grain fed Ujumqin sheep) muscle’s longissimus dorsi. Two breeds three kinds Mongolian sheep muscle’s longissimus dorsi IMF content and fatty acids were analyzed by gas chromatography after methyl esterification. The result reveals that: (1) The IMF content in pastoral of mongolian and Ujumqin sheep muscles was between winter and summer seasons observed extreme differences (p<0.01), but no extreme differences (p>0.01) in grain fed Ujumqin sheep. (2) The result showed that there were 29 identified fatty acids in the muscle’s longissimus dorsi means of winter season pastoral Mongolian, Ujumqin and grain fed Ujumqin sheep, where in the content of palmitic acid, stearic acid and oleic acid were 71.45%, 73.17%, 72.02% of the total content of fatty acids respectively. Also saturated fatty acids accounted for 44.49%, 46.27%, 45.37%; monounsaturated fatty acids accounted for 35.68%, 36.09%, 35.9; polyunsaturated fatty acids accounted for 8.18%, 8.33%, 9.32% respectively. In the summer muscle’s longissimus dorsi means of Mongolian, Ujumqin and grain fed Ujumqin sheep were 31, 31, 26 identified fatty acids, where in the content of palmitic acid, stearic acid and oleic acid were 75.96%, 77.17%, 72.79% of the total content of fatty acids respectively. Also saturated fatty acid accounted for 48.35%, 48.09%, 46.31; monounsaturated fatty acids accounted for 36.46%, 37.66%, 36.54; polyunsaturated fatty acids accounted for 7.07%, 7.43%, 8.05% respectively. Therefore, positive feature of pastoral Mongolian and Ujumqin sheep in muscle’s longissimus dorsi means that levels of the nutritionally important long chain PUFA EPA C20:5, DHA C22:6 was in winter 1.2-1.8%; in summer of the total content of fatty acids 1-1.2% respectively. But grain fed Ujumqin sheep muscle’s different parts means only identified long chain PUFA EPA C20:5 was in winter and summer 0.8% of the total content of fatty acids and lower than pastoral Mongolian and Ujumqin sheep 1%. Монгол хонины нурууны булчин махны тосны хүчлийн бүрдлийн судалгаа Энэхүү судалгаагаар өвөл болон зуны улирлын 2 үүлдэрийн 3 төрлийн Монгол хонины (Бэлчээрийн Монгол, Үзэмчин болон суурин маллагаатай Үзэмчин) нурууны булчин маханд (M. longissimus dorsi) тос болон тосны хүчлийн бүрдлийг харьцуулан судалсан болно. Дээрх 3 төрлийн хонины нурууны булчин эдийн тосыг ялган хэмжээг тогтоож, метил эфиржүүлсний дараа хийн хромотаграфаар тосны хүчлийн бүрэлдэхүүнийн тодорхойлсон. Булчин эдийн тосны агууламжийн үр дүн: Бэлчээрийн Монгол болон Үзэмчин хонины гуяны булчин эдийн тосны агууламж нь өвөл болон зуны улирлын хооронд хэт их утга (p<0.01) илэрсэн. Тосны хүчлийн бүрэлдэхүүний үр дүн: Өвлийн улирлын бэлчээрийн Монгол, Үзэмчин болон суурин маллагаатай Үзэмчин хонины longissimus dorsi булчин эдэд нийт тосны 89.35%, 91.19%, 90.6% -ийг 29 төрлийн тосны хүчил бүрдүүлж түүнээс пальмитины (C16:0), стеарины (C18:0), олеины хүчлүүд (C18:1) хүчлүүд 71.45%, 73.17%, 72.02%-ийг эзэлж байв. Зуны улиралд хонины нурууны булчин эдийн нийт тосны 91.88%, 93.18%, 90.9% -ийг 26-31 төрлийн тосны хүчил бүрдүүлж түүнээс пальмитины (C16:0), стеарины (C18:0), олеины хүчлүүд (C18:1) хүчлүүд 75.96%, 77.17%, 72.79%-ийг тус тус бүрдүүлж байна. Өвлийн улирлын бэлчээрийн Монгол, Үзэмчин болон суурин маллагаатай Үзэмчин хонины нурууны булчин эдийн дундаж ханасан тосны хүчил 44.49%, 46.27%, 45.37%’; мониен хүчил 35.68%, 36.09%, 35.9%; полиен хүчил 8.18%, 8.33%, 9.32%; Зуны улиралд ханасан хүчил 48.35%, 48.09%, 46.31%; мониен хүчил 36.46%, 37.66%, 36.54%; полиен хүчил 7.07%, 7.43%, 8.05% тус тус агуулагдаж байв. Эмчилгээний өндөр ач холбогдолтой гэгдээд байгаа EPA C20:5 болон DHA C22:6 олон холбоот тосны хүчлүүд бэлчээрийн Монгол болон Үзэмчин хонинд эдгээр хүчлийн нийлбэр өвлийн улирал 1.2-1.8%, зуны улиралд 1-1.2% агуулагдаж суурин маллагаатай Үзэмчин хонины нурууны булчин махнаас 1% орчим өндөр агуулагдаж байгаа бэлчээрийн хонины махны ач холбогдлыг илэрхийлэх үндэслэлтэй. Түлхүүр үг: Монгол хонь, Үзэмчин хонь, тосны хүчил, өвөл, зун

The relationship between dietary intakes and plasma concentrations of polyunsaturated fatty acids in school-aged children from the ALSPAC cohort

An adequate intake of polyunsaturated fatty acids (PUFAs) plays a vital role in human health. Therefore, it is important to assess PUFA intakes in different populations and validate them with biomarkers, but only a few small studies are in paediatric populations. We calculated the dietary intake of PUFAs and their main food sources in children and assessed associations between reported PUFA intakes and plasma proportions. Dietary intakes of 7-year-old children (n=8,242) enrolled in the Avon Longitudinal Study of Parents and Children were calculated from parental-completed food frequency questionnaire. Plasma PUFAs were measured in 5,571 children 8 months later and 4,380 children had complete dietary and plasma data. The association between dietary and plasma PUFAs proportions were estimated using Spearman’s correlation coefficients, quintile cross-classification and Cohen’s kappa coefficients. Mean total PUFA intake was 13.2g/day (sd4.2), contributing 6.5% of total energy intake; n-6 PUFA contributed 5.2% and n-3 PUFA 0.7%. The n-6:n-3 ratio was 7.9:1. Mean intakes of eicosapentaenoic acid and docosahexaenoic acid (DHA) were 35.7mg/day and 49.7mg/day, respectively. Most n-3 and n-6 PUFA intakes were weakly correlated with their respective plasma lipids (0.07≤ r ≤0.16, p<0.001). The correlation between dietary and plasma DHA was stronger though (r=0.34, p<0.001), supported by a modest level of agreement between quintiles (k=0.32). The results indicate that the FFQ was able to reasonably rank the long-chain PUFA, DHA, in this paediatric population. Public health initiatives need to address the suboptimal ratio of n-6:n-3 PUFAs and very low n-3 long-chain PUFA intakes in school-aged children in the UK.

Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineated in the different organs. The liver showed an oxidant/antioxidant profile and lipid pathways widely modulated by PUFA and vitamin E administration; on the other hand, the testis’ oxidative profile rather than its lipid profile seemed to be particularly affected, an outcome opposite to that of the brain (modulation operated by dietary PUFA).

Dietary Reference Intakes Based on Chronic Disease Endpoints: Outcomes from a case study workshop for omega 3’s EPA and DHA

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a one-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.

Maternal and child fatty acid desaturase genotype as determinants of cord blood long-chain PUFA (LCPUFA) concentrations in the Seychelles Child Development Study

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

Diet Regulation of Long-Chain PUFA Synthesis: Role of Macronutrients, Micronutrients, and Polyphenols on Δ-5/Δ-6 Desaturases and Elongases 2/5

ABSTRACT Deficiencies in the n–3 (ω-3) long-chain PUFAs (LC-PUFAs) EPA and DHA are associated with increased risk for the development of numerous diseases. Although n–3 LC-PUFAs can be obtained by consuming marine products, they are also synthesized endogenously through a biochemical pathway regulated by the Δ-5/Δ-6 desaturase and elongase 2/5 enzymes. This narrative review collates evidence from the past 40 y demonstrating that mRNA expression and activity of desaturase and elongase enzymes are influenced by numerous dietary components, including macronutrients, micronutrients, and polyphenols. Specifically, we highlight that both the quantity and the composition of dietary fats, carbohydrates, and proteins can differentially regulate desaturase pathway activity. Furthermore, desaturase and elongase mRNA levels and enzyme activities are also influenced by micronutrients (folate, vitamin B-12, vitamin A), trace minerals (iron, zinc), and polyphenols (resveratrol, isoflavones). Understanding how these various dietary components influence LC-PUFA synthesis will help further advance our understanding of how dietary patterns, ranging from caloric excesses to micronutrient deficiencies, influence disease risks.

Association between dietary intake and serum biomarkers of long-chain PUFA in Japanese preschool children

Objective: Recent research supports the importance of PUFA intake in children, particularly of EPA and DHA; however, few verified methods to assess whether PUFA intake is adequate are available. Design: We assessed the correlation between serum PUFA and lipid concentrations with seafood and PUFA intake measured using a brief-type self-administered diet history questionnaire for Japanese preschool children (BDHQ3y). Setting: Single centre birth cohort in Japan. Participants: A total of 152 36-month-old Japanese children. Results: Average dietary intake of daily seafood, EPA and DHA was 13·83 (sd 10·36) g, 49·4 (sd 43·5) mg and 98·3 (sd 64·6) mg, respectively. Significant weak-to-moderate correlations were observed between dietary intake and serum EPA (Spearman rho = 0·41, P < 0·001; Pearson r = 0·44, P < 0·001); DHA (Spearman rho = 0·40, P < 0·001; Pearson r = 0·42, P < 0·001) and AA (arachidonic acid) (Spearman rho = 0·33, P < 0·001; Pearson r = 0·32, P < 0·001), whereas no significant correlation was observed for dihomo-γ-linolenic acid (DGLA) (Spearman rho = 0·06, P = 0·484; Pearson r = 0·07, P = 0·387). Correlations between seafood intake and serum EPA and DHA were also moderate (0·39–0·43). A negative correlation between serum TAGs and serum EPA, as well as positive correlations between serum cholesterol (total cholesterol, LDL and HDL) with serum EPA and DHA were observed, whereas no significant correlations between seafood intake and serum lipid profiles. Based on this model, we estimated 61–98 g/week of seafood intake is required to meet current EPA/DHA intake recommendations by the WHO (100–150 mg/d). Conclusions: For children of 2–4 years of age, weekly intake of 61–98 g of seafood is required to meet WHO recommendations of EPA/DHA intake.

Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8–11-year-old Danish children?

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8–11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children’s cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.