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Linolenic acid deficiency.

Linolenic acid deficiency has not been demonstrated clearly in warm blooded animals, yet circumstantial evidence suggests that n-3 fatty acids may have functions in these animals. The fact that several species of fish definitely require dietary n-3 fatty acids indicates that n-3 fatty acids have important and specific functions in these animals and suggests that such functions may also be present in warm blooded animals. It is also true that n-3 fatty acid distribution in tissues of birds and mammals appears to be under strict metabolic control, and that this complex metabolic control mechanism apparently has survived evolutionary pressure for a very long time. So far, attempts to produce linolenic acid deficiency in mammals have not revealed an absolute requirement for n-3 fatty acids. If functions for n-3 fatty acids do exist in warm blooded animals, it seems probable that they may be located in the cerebral cortex or in the retina, because these tissues normally contain high concentrations of n-3 fatty acids.

Animals↗

The effect of essential fatty acid deprivation on the metabolic transformations of [1(-14)C]linolenate in developing rat brain.

Linolenic acid undergoes rapid metabolism in the brain of 21-day-old rats. Radioactivity is rapidly transferred from linolenic acid to the C20 (n--3) fatty acids while that in docosapentaenoic acid (22 : 5 n--3) and docosahexaenoic acid (22 : 6 n--3) gradually increases. A greater proportion of the radioactivity is associated with the polyunsaturated and less with saturated and monounsaturated fatty acids in essential fatty acid-deprived rats relative to controls.

Animals↗

The protective effects of dietary fish oil on focal cerebral infarction.

The protective effect of the (n-3) fatty acids in menhaden fish oil on acute cerebral ischemia was investigated in cats. Cerebral ischemia was produced by ligation of the left middle cerebral artery of cats fed either a basal diet of feline cat chow or the basal diet supplemented with 8% of the calories as menhaden oil for 18-24 days. Fatty acids esters of 20:5 (n-3) were increased and the 18:2 (n-6) decreased in the heart and liver of cats fed supplemental fish oil, but the brain lipid showed no effect of the diet. We found that the neurological deficit and the volume of brain infarction in the group treated with fish oil was less than that of the control group. The present findings suggest that moderate dietary supplements of fish oil may be beneficial in the prophylactic treatment of ischemic cerebral vascular disease.

Animals↗

Antimicrobial Resistance Phenotypes and Genotypes of Cecal Digesta Escherichia coli of Pullets Fed Omega-3 Fatty Acids or Yeast Bioactives (Glycobolites).

Antimicrobial resistance (AMR) is a significant threat to poultry production and food safety. In laying hens, commensal Escherichia coli can serve as a reservoir of AMR and virulence genes. Although omega-3 fatty acids (N-3 FAs), yeast bioactives (YB), and spacing allowance (SA) influence gut health and immunity, their combined effects on AMR profiles of gut bacteria remain unclear. A total of 2,832 chicks were raised in enriched cages under high (HSA, 348&#xa0;cm2/bird) or low (LSA, 284&#xa0;cm2/bird) SA and fed a control diet (C), C+3% N-3 FA, or C+0.05% YB. At 4, 16, and 35&#xa0;weeks of age (woa), cecal contents were cultured on ChromoCult agar to isolate E. coli. Susceptibilities of isolates to 14 antibiotics were determined. Of the 428 isolates, 35.7% were resistant to at least one antimicrobial, and overall, AMR prevalence decreased with age (P&#xa0;<&#xa0;0.05). At each of 4 and 16 woa, N-3 FA-fed birds showed the lowest prevalance of ampicillin-resistant (P&#xa0;<&#xa0;0.05). The prevalence of streptomycin resistance was higher in N-3 FA than in YB-fed birds at 16 woa (P&#xa0;=&#xa0;0.02) but lower than in control-fed birds. Whole-genome sequencing and analysis of 237 selected isolates identified 19 antimicrobial resistance genes (ARGs) and 29 plasmids, with the distribution of 15 (78.9%) ARGs and 19 (65.5%) plasmid replicons affected by either diet, SA, or age (P&#xa0;<&#xa0;0.05). Several virulence genes were identified in sequenced E. coli isolates, with the prevalence of those encoding fimbriae, pili, protectin, and toxins being higher in younger pullets (P&#xa0;<&#xa0;0.05). Overall, isolates of phylogroups A and B1 were predominant; however, at 4 woa, phylogroup D isolates were most prevalent, depending on diet and SA (P&#xa0;<&#xa0;0.05). Isolates of serotype O23:H16, ST2 were the most prevalent. Of the 237 sequenced isolates, 13 were related to human extraintestinal pathogenic Escherichia coli (ExPEC) strains. Overall, these findings suggest that N-3 FA YB and SA modulate AMR and virulence genotypes of E. coli in laying hens, highlighting their potential use of these agents in mitigating AMR.

Antimicrobial resistance↗

[Effects of conjugates of linolenic acid and erucic acid on rat cardiac and liver lipids].

Cardiac and liver lipids (triglycerides and phospholipids) were analyzed in weanling rats fed for 8 days diets containing 15% by weight of four different lipid mixtures: trierucin and peanut oil (1/1), trierucin and linseed oil (1/1), triolein and peanut oil (1/1), triolein and linseed oil (1/1). Linolenic acid (8 cal% of the diet) does not influence the steatogenic effect of erucic acid (15 cal% of the diet) on the myocardium but seems to increase the hepatic conversion of erucic acid into shorter monoenes (C 18:1 mainly). The (n-6), (n-3) fatty acid spectra in heart and liver phospholipids are strongly affected when linolenic acid is added to the diet whereas erucic acid has little effect.

Animals↗

Seafood and polyunsaturated fatty acid intake and age-related hearing loss: a cross-sectional study conducted in Japan.

BACKGROUND: Age-related hearing loss (ARHL) is a common condition associated with dementia, social isolation, and reduced quality of life. N-3 polyunsaturated fatty acids (N-3 PUFAs), mainly derived from seafood, have been hypothesized to protect against ARHL through anti-inflammatory and antioxidant effects. However, evidence remains inconsistent. This cross-sectional study examined the association of seafood and dietary fatty acid intakes with ARHL in a Japanese population with high seafood consumption. METHODS: A total of 13,908 adults aged 50-79 years from the Tohoku Medical Megabank Project Cohort Study were included. Hearing thresholds were measured by pure-tone audiometry at 500, 1,000, 2,000, and 4,000 Hz. Dietary intake was assessed using a validated food frequency questionnaire. Seafood, N-3 PUFA, and saturated fatty acid (SFA) intakes were categorized into quartiles. Multivariable linear regression was used to estimate adjusted mean differences in hearing thresholds. RESULTS: In men, higher SFA intake was significantly associated with lower hearing thresholds at 1,000 Hz (Q4 vs. Q1: &#x3b2; = -2.23 dB HL, 95% CI: -3.437 to -1.023) and for pure-tone average (&#x3b2; = -1.704 dB HL; 95% CI, -2.872 to -0.536). Seafood and N-3 PUFA intakes were not significantly associated with hearing thresholds. In women, no significant associations were observed. CONCLUSION: In this population with high seafood consumption, seafood and N-3 PUFA intakes were not associated with hearing thresholds. Low SFA intake may be associated with higher hearing thresholds in Japanese men, suggesting that the relationship between dietary fatty acids and ARHL may be complex and may differ by sex.

Age-related hearing loss↗

Leukocyte docosahexaenoic acid in juvenile form of ceroid-lipofuscinosis.

Leukocyte glycerolipid fatty acid compositions were determined in four patients of juvenile form of neuronal ceroid-lipofuscinosis (Battens disease), their parents and age-matched controls. A 54 to 93% reduction in docosahexaenoic acid (22:6, n-3) was noted in patient leukocytes. The parents also showed reduction in docosahexaenoic acid content, but to a lesser degree. The levels of linolenic family (n-6) polyunsaturated fatty acids were unchanged suggesting that the metabolic defect in this disease is specific to the linolenic family (n-3) of fatty acids.

Adolescent↗

Supplementations of docosahexaenoic acid and blueberry suppress a high-fat breakfast-induced postprandial inflammation but only docosahexaenoic acid improves endothelial function in healthy adults: a randomized, double-blind, placebo-controlled crossover intervention study.

Blueberries and n - 3 polyunsaturated fatty acids each can provide protection against inflammation and cardiometabolic disorders. However, the underlying mechanisms are not fully understood. We hypothesized that blueberry and docosahexaenoic acid (DHA) can suppress high fat (HF) meal-induced postprandial inflammation and improve endothelial function. Sixty-two healthy participants (age: 26.8 &#xb1; 1.2 y; BMI: 22.1 &#xb1; 1.2 kg/m&#xb2;) consumed an isoenergetic breakfast (850 kcal) containing 34.7 g mostly animal fat (36% kcal), 25.3 g protein, and 111 g carbohydrate, with or without either 42.2 g blueberry powder (BBP) or 1.76 g DHA in a randomized, double-blind, placebo-controlled crossover intervention study. Blood samples were collected before and 1 h, 3 h and 6 h after breakfast. Monocyte activation, proinflammatory gene expression, cytokine production and endothelial function were assessed. Compared with the placebo control, DHA supplementation suppressed the HF breakfast-induced: expression of IL-1&#x3b2; by 21.6% (P < .01) and prostaglandin-endoperoxide synthase 2 (PTGS2, i.e., cyclooxygenase 2) by 22.8% (P < .01) at 6 h; plasma IL-1&#x3b2; production by 40.1 to 49.8% (P < .01) at 1-6 h; lipoprotein lipase (LPL)-treated blood IL-1&#x3b2; production by 40.9% (P < .0001) at 6 h; and total cholesterol/HDL cholesterol ratio by 2.2% (P < .01) at 3 h and 3.5% (P < .0001) at 6 h. BBP supplementation suppressed LPL-treated blood IL-1&#x3b2; production by 23.1% (P < .05) at 6 h. BBP and DHA also induced postprandial increases in reactive hyperemia index (RHI) scores relative to the fasting baselines, with DHA producing a 13.3% increase compared with placebo at 6 h (P < .05). In conclusion, supplementation with BBP or DHA suppressed the HF meal-induced postprandial inflammation but only DHA improved postprandial endothelial function. This study was registered at clinicaltrails.gov (NCT02472171).

Blueberry↗

Vegan multinutrient supplementation significantly increases Omega-3 index and 25-OH-vitamin D status: a randomized, double-blind, placebo-controlled trial in healthy young vegans.

In this randomized, double-blind, placebo-controlled trial, 72 healthy vegan adults (aged 19-57 years) received a multinutrient supplement consisting of a vitamin and mineral supplement (providing 26 &#xb5;g vitamin D) and an omega-3 supplement administered in either a single dose (EPA 98.7 mg, DHA 171.0 mg, additional vitamin D 36 &#xb5;g, vitamin E 3.7 mg) or a double dose (EPA 197.4 mg, DHA 342.0 mg, additional vitamin D 72 &#xb5;g, vitamin E 7.4 mg) or placebo capsules for 4 months. Nutrient biomarkers were assessed at baseline and at the end of the intervention after 4 months. An analysis of covariance was employed to test for between-group differences (p < 0.05) and adjusted for multiple testing using the Bonferroni-Holm method. Compared to the control group, which showed on average a significant decline in both the omega-3-index and 25-hydroxyvitamin D, participants in both intervention groups demonstrated significant increase in these parameters (p < 0.001). Although the double dose group exhibited numerically greater increases in omega-3 index and vitamin D compared to the simple dose group, the differences between these dosing regimens were not statistically significant. As expected, vitamin E levels remained unchanged, reflecting its inclusion solely for antioxidative protection in the omega-3 supplement rather than as a critical nutrient in vegan diets. In conclusion, supplementation significantly improved omega-3 and vitamin D status in healthy vegans, with no significant benefit from doubling the dose. Although clinical endpoints were not evaluated, improved nutrient status may have potential implications for health. The study has been registered at the German Clinical Trials Register (DRKS00028151).

Humans↗

The effect of hibernation on the positional distribution of ethanolamineglycerophospholipid fatty acids in hamster brain membranes.

Microsomal and myelin membrane fractions were prepared from the brains of warm-adapted (room temperature) and hibernating Syrian Hamsters (Mesocricetus auratus). Ethanolamineglycerophospholipids were isolated and subjected to a fractionation scheme to separate the fatty acids of the plasmenylethanolamine and the phosphatidylethanolamine 1 and 2 positions. The major changes in microsomal phosphatidylethanolamine with hibernation were relative increases in 18:1 at the 1 position and 20:4(n-6) in the 2 position. In myelin, 18:1 increased and 18:0 decreased at the 1 position while the 2 position showed an increase in 16:0 and a decrease in 22:6(n-3). Plasmenylethanolamine fatty acids also changed in microsomes and myelin although the magnitudes were not as great and confined to longer chain fatty acids. In both membranes, fatty acid alterations were position-specific, and no new types of fatty acids were introduced at any position.

Animals↗

Inhibition of prostaglandin biosynthesis by eicosapentaenoic acid.

Eicosapentaenoic acid [20 : 5 (n-3)] is not oxidized by the purified cyclooxygenase from sheep vesicular glands in the conditions of low peroxide tone in which arachidonate [20 : 4 (n-6)] is rapidly oxygenated. When the level of peroxide in incubation mixtures is allowed to rise, there is a dramatic change in reactivity of the cyclooxygenase to react with 20 : 5 (n-3) at one-halt the rate and one-third the extent observed with 20 : 4 (n-6). Overall, the low peroxide levels expected in vivo would most probably cause the (n-3) type of fatty acid to be a general inhibitor of prostaglandin formation, through both reversible and irreversible actions at the enzyme site.

Animals↗

Proteomic and Phosphoproteomic Signatures Link Molecular Remodeling to Behavioral Outcomes Following Elderberry and DHA Supplementation in Aging Mice.

Background: Aging is a risk factor for Alzheimer's disease and related dementias, which are associated with synaptic dysfunction and cognitive decline. Elderberry (Sambucus spp.) is rich in anthocyanins with antioxidant and anti-inflammatory properties. Docosahexaenoic acid (DHA), an essential fatty acid, plays a key role in neuronal membrane integrity during brain aging. However, it remains unclear whether elderberry and DHA exert overlapping or distinct effects on brain aging and how these relate to molecular signaling. This study aimed to characterize molecular signatures induced by dietary supplementation and to determine their relationships with behavioral outcomes. Methods: 44-week-old male C57BL/6J mice were randomly assigned to control, elderberry, DHA, or combined diets for 12 weeks. Behavioral testing assessed anxiety-like behavior, spatial learning and memory. Brain tissues underwent proteomic and phosphoproteomic profiling and fatty-acid analysis. Data were analyzed using Ingenuity Pathway Analysis to identify enriched pathways, upstream regulators, and functional associations. Results: Elderberry as well as DHA supplementation induced targeted remodeling of the proteome and phosphoproteome, with pathway enrichment involving synaptogenesis, glutamatergic signaling, and long-term potentiation. Upstream-regulator analysis predicted elderberry-associated CDK5 signaling, accompanied by reduced MAPT/Tau phosphorylation at selected sites, whereas DHA supplementation was associated with CAMK-related signaling. DHA supplementation altered fatty-acid composition, increasing the n-3/n-6 ratio. Elderberry reduced anxiety-like behavior and improved target-directed search during the Barnes maze probe test. Molecular signatures were examined in relation to the measured behavioral outcomes. Conclusions: Elderberry and DHA are associated with distinct molecular networks related to synaptic function and behavioral outcomes in the aging male mouse brain. These findings support further investigation of elderberry and DHA as dietary interventions targeting molecular and behavioral features of brain aging.

Animals↗

[Treatment of hypercholesterolemia in the male rat by introduction of soya oil supplemented or not with sardine oil in the diet].

Substituting soya oil for lard considerably reduced hypercholesterolemia in the male rat with induced hypercholesterolemia due to a dietary overlead of cholesterol and sodium deoxycholate. The decrement was more marked when a mixture of 80 p. 100 soya oil + 20 p. 100 sardine oil replaced the lard. This improvement of the hypocholesterolemic effect by adding sardine oil to soya oil was due to the long-chain fatty acids (mainly C20:5 and/or C22:5 n-3 in the fish oil).

Animals↗

Associations of red blood cell fatty acids with personality traits: 10-year follow-up in the Kibbutzim Family Study (KFS).

BACKGROUND: The ability of hostility and type-A personality to predict cardiovascular outcomes makes understanding antecedents of these personality traits an important public health objective. OBJECTIVES: This study aimed to examine whether blood-measured fatty acids (the exposure) are associated with hostility and type-A personality (the outcome), while accounting for lifestyle, sociodemographic factors, and polygenic background. METHODS: Personality traits, sociodemographic, and lifestyle data were obtained in 1992-1993 from 452 family members living in kibbutz settlements in Israel (visit 1) and remeasured 8 to 10 y later in 379 individuals (visit 2). Red blood cell (RBC) fatty acid concentrations were determined in visit 1 by gas chromatography. Longitudinal associations of visit 1 fatty acids with visit 2 personality traits were examined using linear models, before and after controlling for baseline personality scores. The contribution of environmental factors to personality scores beyond heritability was estimated by variance decomposition. RESULTS: In longitudinal analysis, 1% increase in visit 1 total n-6 (&#x3c9;-6) fatty acid was associated with a 0.328-unit decrease in visit 2 type-A score [95% confidence interval (CI): -0.571, -0.085]. After adjustment for baseline personality levels, the association was slightly attenuated (&#x3b2;= -0.204; CI: -0.399, -0.009). One percent higher total n-6 was also associated with 1.119 units lower visit 2 hostility score (CI: -2.777, 0.038; P = 0.055). Finally, independent of the genetic contribution (32%-38% of adjusted variability in hostility and type-A personality), 1% increase in total n-3 and total n-6 was associated with 2.539 (CI: -3.907, -1.171) and 0.201 (CI: -0.365, -0.037) units lower hostility and type-A scores, respectively. CONCLUSIONS: Higher RBC total n-6 fatty acid concentrations are associated with lower type-A personality scores. After adjustment for baseline personality levels, the associations between total n-6 and hostility and between total n-3 and hostility are attenuated. These findings support further investigation of the relationship between fatty acid biology and personality traits using study designs better suited to causal inference.

Humans↗

In vitro lipid metabolism in the rat pancreas. III. Effects of carbamylcholine and pancreozymin on the turnover of phosphatidylinositols, 1,2-diacylglycerols and phosphatidylcholines.

1. The turnover of phosphatidylinositols and other glycerolipids was examined in rat pancreatic fragments incubated in the presence of carbamylcholine and pancreozymin used at a concentration inducing maximal alpha-amylase hypersecretion. 2. In stimulated tissue, [1-14C]acetate-labeled fatty acids were incorporated into phosphatidylinositols, 1,2-diacylglycerols, and phosphatidic acids in preference to phosphatidylcholines, phosphatidylethanolamines, triacylglycerols, monoacylglycerols, and free fatty acids. Variations in the percent distribution of 14C among fatty acids and in specific activity of individual fatty acids in each lipid class suggested that the secretagogues reduced selection of newly synthesized 1,2-diacylglycerols which occurred in the resting state before their incorporation into phosphatidylinositols. Secretagogues also promoted recycling of endogenous 1,2-diacylglycerols (produced from hydrolysis of unlabeled glycerolipids) for the biosynthesis of phosphatidylinositols. 3. Increased rate of incorporation of [1-14C]palmitate, [1-14C]linoleate, [1-14C]arachidonate and [1(3)(n)-3H]glycerol into phosphatidylinositols was detrimental to phosphatidylcholines. 4. The lipolytic effects of carbamylcholine and pancreozymin as illustrated by the release of 1,2-diacylglycerols and free fatty acids, were markedly inhibited in calcium-free medium enriched with 1 mM EGTA but increased turnover of phosphatidylinositols as determined from incorporation of radioactive precursors was only moderately affected.

Animals↗

Methyl-directed desaturation of arachidonic to eicosapentaenoic acid in the fungus, Saprolegnia parasitica.

The lipids of Saprolegnia parasitica contain 5,8,11,14,17-eicosapentaenoic acid as major constituent. No other acid having (n-3) structure was detected, but 5,8,11,14-eicosatetraenoic (arachidonic) acid and its common precursors of (n-6) structure are present in significant amounts. During rapid growth of the organism, [1-14C]acetate was efficiently incorporated into fatty acids. Arachidonic acid was labeled after 2 h to nearly the same extent as any precursor acid and 14C in eicosapentaenoic acid reached this level within 6 h. Results of incubations with labeled fatty acids indicated that, in S. parasitica, oleic, linoleic, (6,9,12)-linolenic and arachidonic acids are major intermediates in the pathway to eicosapentaenoic acid. Methyl-directed desaturation of (n-6) to (n-3) acids does not occur with C18 acids but is specific for the polyunsaturated C20 chain length. Arachidonic acid is the direct precursor of eicosapentaenoic acid.

Acetates↗

Age-associated variation in lipid composition and nutritional quality of the invasive bivalve Anadara kagoshimensis from the Sea of Azov.

This study examined age-associated variation in lipid composition and nutritional quality in the invasive clam Anadara kagoshimensis from the Sea of Azov. Fatty acid and sterol compositions were determined by gas chromatography in clams assigned by sclerochronology to five age classes (2-6&#xa0;years). Several lipid-quality indices, including PUFA/SFA, IA, IT, hH, and HPI, exhibited their most favorable mean values in the 4-year group. The highest condition index (13.7) and the lowest n-3/n-6 ratio (1.1) were observed in the small and unbalanced group of 6-year-old clams. An exploratory linear discriminant analysis (LDA) workflow was used to examine whether primary lipid variables and mathematically derived composite features could enhance age-group separation. LDA based on primary variables yielded 78% leave-one-out classification within the present dataset. Data-driven composite-feature construction increased the within-dataset classification to 100% and graphical group separation to 85%, the values with yet restricted predictive accuracy due to the limited dataset. The results provide baseline information on age-associated lipid variation in A. kagoshimensis and illustrate a proof-of-concept workflow that can be tested in future studies using larger, balanced samples and special validation approaches.

Arcidae↗

Forebrain fatty acid composition during development in protein-calorie and essential fatty acid deficiencies in the rat.

Rats were fed three different dietary levels of essential fatty acids (EFA), 3.0, 0.75 and 0.1 cal%, representing normal, subnormal and severely deficient dietary intakes. From the animals kept on these diets, with a protein content of 16 cal%, 3-month-old females were randomly selected to be fed diets with only 6 cal% protein but with unchanged amounts of EFA. The rats were then mated, and the effects of the diets were studied in the forebrains of their offspring. The growth and the fatty acid patterns of the ethanolamine phosphoglyceride and total phosphoglyceride fractions were studied during the first 60 days of life. Addition of protein-calorie deficiency to rats severely undernourished in EFA mitigated the biochemical signs of EFA deficiency. In EPG the developmental pattern with a decrease of 20:4 (n-6) and an increase of 22:6 (n-3) was retarded between 11 and 21 days of age in the protein-calorie deficient groups suggesting a delay in the maturation of the forebrain.

Aging↗