Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats.

BACKGROUND: Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS. AIM: To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats. METHODS: Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05. RESULTS: Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed. CONCLUSION: The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.

Feeding docosahexaenoic acid and arachidonic acid during suckling and weaning contributes to oral tolerance development by beneficially modulating the intestinal cytokine and immunoglobulin levels in an allergy-prone Brown Norway rat model.

BACKGROUND: Suckling and weaning arachidonic acid (ARA)+docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown. OBJECTIVE: We aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development. METHODS: Allergy-prone Brown Norway dams were randomized to a control (0%ARA, 0%DHA) or ARA+DHA diet (0.45%ARA, 0.8%DHA) during suckling (0-3wks). At weaning (3-8wks), offspring were randomized to a control (0%ARA, 0%DHA) or ARA+DHA diet (0.5% ARA, 0.5%DHA). At 3wks, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for 5 consecutive days. At 7wks, all offspring received an intraperitoneal OVA injection. At 8wks, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related sIgA and cytokines, ileum phospholipid and triglyceride fatty acid compositions and fecal calprotectin. RESULTS: Weaning ARA+DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P <0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA+DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile (higher levels of mucosal IL-2 (P =0.049) and sIgA (P =0.033)). OVA treatment resulted in a lower level of mucosal IL-6 (P =0.026) regardless of dietary interventions. Offspring fed ARA+DHA during suckling and/or weaning had a higher level of mucosal TGF-ß after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P =0.04). CONCLUSIONS: Early-life dietary ARA+DHA supplementation to allergy-prone rats enhanced the DHA level in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2 and TGF-ß levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.

Structural and functional analysis of plant ELO-like elongase for fatty acid elongation.

ELO-like elongase is a condensing enzyme elongating long chain fatty acids in eukaryotes. Eranthis hyemalis ELO-like elongase (EhELO1) is the first higher plant ELO-type elongase that is highly active in elongating a wide range of polyunsaturated fatty acids (PUFAs) and some monounsaturated fatty acids (MUFAs). This study attempted using domain swapping and site-directed mutagenesis of EhELO1 and EhELO2, a close homologue of EhELO1 but with no apparent elongase activity, to elucidate the structural determinants critical for catalytic activity and substrate specificity. Domain swapping analysis of the two showed that subdomain B in the C-terminal half of EhELO1 is essential for MUFA elongation while subdomain C in the C-terminal half of EhELO1 is essential for both PUFA and MUFA elongations, implying these regions are critical in defining the architecture of the substrate tunnel for substrate specificity. Site-directed mutagenesis showed that the glycine at position 220 in the subdomain C plays a key role in differentiating the function of the two elongases. In addition, valine at 161 and cysteine at 165 in subdomain A also play critical roles in defining the architecture of the deep substrate tunnel, thereby contributing significantly to the acceptance of, and interaction with primer substrates.

Dietary supplementing South African indigenous rams with flaxseed oil and ascorbic acid improves cryopreserved semen quality and in vitro fertility.

The purpose of this study was to evaluate how ascorbic acid with dietary flaxseed oil affects the quality and fertility of cryopreserved ram sperm in South African indigenous rams. Treatment diets were supplemented 60 days before semen collection to afford proper spermatogenesis, adaptation to the feed formulated and fed throughout the study. Semen was collected with the use of artificial vagina following dietary supplementation with five treatment diets (neg. cont. - negative control, pos. cont. - positive control, FLO - 5% Flaxseed oil, ASA - 4% Ascorbic acid, and FLO + ASA). Semen was then extended using tris-based extender and cryopreserved using the programmable freezer (CBS Freezer 2100 series, Laboratory consumables & chemical suppliers, America). Ovaries were collected from a neighbouring slaughter house and conveyed to the lab in 0.9% saline at 37 °C. Data (sperm parameters and in vitro fertility) was then exposed to the GLM (General Linear Model) in Minitab 17. Pearson's correlation coefficient was utilized to investigate the relationship between cryopreserved sperm quality and in vitro fertility. The student Least Significant Difference Test was used to separate the treatment means, and differences were accepted when the p-value was less than 0.05. The FLO + ASA group had higher (p < 0.05) progressive (36.33 ± 1.87), total (88.24 ± 2.24), rapid motility (27.52 ± 1.74), intact plasma membrane (75.67 ± 2.08), total fertilization (65.98 ± 7.39), and total cleavage (66.19 ± 6.50) when compared to other treatment groups. Total fertilization rate had a medium significant (p < 0.001) medium correlation with the progressive motility (r2 = 0.435), total motility (r2 = 0.447) and rapid motility (r2 = 0.409). In conclusion, dietary flaxseed and ascorbic acid (FLO + ASA) improves cryopreserved semen quality, in vitro fertilization rate, and the total cleavage rate. Noteworthy, the progressive, total and rapid motility play a crucial in the in vitro fertilization rate.

Optimized spray-dried conditions' impact on fatty acid profiles and estimation of in vitro digestion of spray-dried chia/fish oil microcapsules.

Long-chain polyunsaturated fatty acids (LCPUFA) are of interest due to their potential health properties and have a significant role in reducing the risk of various chronic diseases in humans. It is commonly used as a supplement. However, lipid oxidation is an important negative factor caused by environmental, processing, and limited water solubility of LCPUFA, making them difficult to incorporate into food products. The objective of this research work was to prevent oxidation, extend shelf life, enhance the stability of fatty acids, and to achieve controlled release by preparing spray-dried powder (SDM). For spray-drying, aqueous emulsion blends were formulated using a 1:1 ratio of chia seed oil (CSO) and fish oil (FO) and using a laboratory-scale spray-dryer with varying conditions: inlet air temperature (IAT, 125-185 °C), wall material (WM, 5-25%), pump speed (PS, 3-7 mL/min), and needle speed (NS, 3-11 s). The maximum alpha-linolenic acid (ALA) content was 33 ± 1%. The highest values of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the microcapsules were 8.4 ± 0.4 and 13 ± 1%, respectively. Fourier transform infrared and X-Ray diffraction analysis results indicated that SDM was successfully formulated with Gum Arabic and maltodextrin (MD). The blending without encapsulation of CSO and FO was digested more efficiently and resulted in more oil being released with simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and SGF + SIF conditions without heating. No significant changes were observed for saturated, monounsaturated, and LCPUFA, whether exposed or not to gastrointestinal conditions. However, compared to the release of SDM, it can be useful for designing delivery systems for the controlled release of essential fatty acids.

Multifactor Analyses of Frontal Cortex Lipids in the APP/PS1 Model of Familial Alzheimer's Disease Reveal Anomalies in Responses to Dietary n-3 PUFA and Estrogenic Treatments.

Brain lipid homeostasis is an absolute requirement for proper functionality of nerve cells and neurological performance. Current evidence demonstrates that lipid alterations are linked to neurodegenerative diseases, especially Alzheimer's disease (AD). The complexity of the brain lipidome and its metabolic regulation has hampered the identification of critical processes associated with the onset and progression of AD. While most experimental studies have focused on the effects of known factors on the development of pathological hallmarks in AD, e.g., amyloid deposition, tau protein and neurofibrillary tangles, neuroinflammation, etc., studies addressing the causative effects of lipid alterations remain largely unexplored. In the present study, we have used a multifactor approach combining diets containing different amounts of polyunsaturated fatty acids (PUFAs), estrogen availabilities, and genetic backgrounds, i.e., wild type (WT) and APP/PS1 (FAD), to analyze the lipid phenotype of the frontal cortex in middle-aged female mice. First, we observed that severe n-3 PUFA deficiency impacts the brain n-3 long-chain PUFA (LCPUFA) composition, yet it was notably mitigated by hepatic de novo synthesis. n-6 LCPUFAs, ether-linked fatty acids, and saturates were also changed by the dietary condition, but the extent of changes was dependent on the genetic background and hormonal condition. Likewise, brain cortex phospholipids were mostly modified by the genotype (FAD>WT) with nuanced effects from dietary treatment. Cholesterol (but not sterol esters) was modified by the genotype (WT>FAD) and dietary condition (higher in DHA-free conditions, especially in WT mice). However, the effects of estrogen treatment were mostly observed in relation to phospholipid remodeling in a genotype-dependent manner. Analyses of lipid-derived variables indicate that nerve cell membrane biophysics were significantly affected by the three factors, with lower membrane microviscosity (higher fluidity) values obtained for FAD animals. In conclusion, our multifactor analyses revealed that the genotype, diet, and estrogen status modulate the lipid phenotype of the frontal cortex, both as independent factors and through their interactions. Altogether, the outcomes point to potential strategies based on dietary and hormonal interventions aimed at stabilizing the brain cortex lipid composition in Alzheimer's disease neuropathology.

Characteristics of infant formula consumed in the first months of life and allergy in the EDEN mother-child cohort.

The evidence regarding the association between infant formula (IF) composition and the prevention of allergy and respiratory diseases remains sparse and inconclusive. This study aimed to evaluate whether some IF characteristics were associated with the risk of allergy or respiratory diseases in childhood. Among 1243 formula-fed children from the EDEN mother-child cohort, IF characteristics concerning long-chain polyunsaturated fatty acids (LCPUFAs) enrichment, prebiotic/probiotic enrichment, and hydrolysis of proteins were identified from the ingredients list. Eczema, wheezing, food allergy, asthma, and allergic rhinitis up to age 8 years were prospectively collected and summarized into four allergic and respiratory multimorbidity clusters. Associations between 4-month IF characteristics and risk of allergy or respiratory diseases were tested using logistic regressions adjusted on main confounders. The consumption of LCPUFA-enriched formula was not linked to allergic and respiratory multimorbidity clusters, but to a lower risk of any allergy, eczema, and wheezing. Probiotic-enriched formula consumption was associated with a lower risk of belonging to the 'Allergy without asthma' cluster (odds ratio [OR] [95% confidence interval, CI] = 0.63 [0.40-0.99]), and consumption of a formula enriched in Bifidobacterium lactis was associated with a lower risk of any allergy (OR [95% CI] = 0.59 [0.41-0.85]). Partially hydrolysed formula (pHF) consumption was associated with a higher risk of belonging to the 'Allergy without asthma' cluster (OR [95% CI] = 2.73 [1.65-4.51]). This study confirms the positive association between pHF consumption and the risk of allergy found in previous observational studies and suggests that consumption of LCPUFA-enriched or probiotic-enriched formula was associated with a lower risk of allergy.

A complete biosynthetic pathway of the long-chain polyunsaturated fatty acids in an amphidromous fish, ayu sweetfish Plecoglossus altivelis (Stomiati; Osmeriformes).

The biosynthetic capability of the long-chain polyunsaturated fatty acids (LC-PUFA) in teleosts are highly diversified due to evolutionary events such as gene loss and subsequent neo- and/or sub-functionalisation of enzymes encoded by existing genes. In the present study, we have comprehensively characterised genes potentially involved in LC-PUFA biosynthesis, namely one front-end desaturase (fads2) and eight fatty acid elongases (elovl1a, elovl1b, elovl4a, elovl4b, elovl5, elovl7, elovl8a and elovl8b) from an amphidromous teleost, Ayu sweetfish, Plecoglossus altivelis. Functional analysis confirmed Fads2 with Δ6, Δ5 and Δ8 desaturase activities towards multiple PUFA substrates and several Elovl enzymes exhibited elongation capacities towards C18-20 or C18-22 PUFA substrates. Consequently, P. altivelis possesses a complete enzymatic capability to synthesise physiologically important LC-PUFA including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) from their C18 precursors. Interestingly, the loss of elovl2 gene in P. altivelis was corroborated by genomic and phylogenetic analyses. However, this constraint would possibly be overcome by the function of alternative Elovl enzymes, such as Elovl1b, which has not hitherto been functionally characterised in teleosts. The present study contributes novel insights into LC-PUFA biosynthesis in the relatively understudied teleost group, Osmeriformes (Stomiati), thereby enhancing our understanding of the complement of LC-PUFA biosynthetic genes within teleosts.

ω-3 Polyunsaturated Fatty Acid Status Testing in Humans: A Narrative Review of Commercially Available Options.

There is an increasing body of evidence supporting a link between low intakes of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) and numerous diseases and health conditions. However, few people are achieving the levels of fish/seafood or eicosapentaenoic acid and docosahexaenoic acid intake recommended in national and international guidelines. Knowledge of a person's ω-3 LCPUFA status will benefit the interpretation of research results and could be expected to lead to an increased effort to increase intake. Dietary intake survey methods are often used as a surrogate for measuring ω-3 PUFA tissue status and its impact on health and functional outcomes. However, because individuals vary widely in their ability to digest and absorb ω-3 PUFA, analytical testing of biological samples is desirable to accurately evaluate ω-3 PUFA status. Adipose tissue is the reference biospecimen for measuring tissue fatty acids, but less-invasive methods, such as measurements in whole blood or its components (e.g., plasma, serum, red blood cell membranes) or breast milk are often used. Numerous commercial laboratories provide fatty acid testing of blood and breast milk samples by different methods and present their results in a variety of reports such as a full fatty acid profile, ω-3 and ω-6 fatty acid profiles, fatty acid ratios, as well as the Omega-3 Index, the Holman Omega-3 Test, OmegaScore, and OmegaCheck, among others. This narrative review provides information about the different ways to measure ω-3 LCPUFA status (including both dietary assessments and selected commercially available analytical tests of blood and breast milk samples) and discusses evidence linking increased ω-3 LCPUFA intake or status to improved health, focusing on cardiovascular, neurological, pregnancy, and eye health, in support of recommendations to increase ω-3 LCPUFA intake and testing.

Accumulation of docosapentaenoic acid (n-3 DPA) in a novel isolate of the marine ichthyosporean Sphaeroforma arctica.

OBJECTIVE: Currently, there is lack of a consistent and highly enriched source for docosapentaenoic acid (n-3 DPA, C22:5), and this work report the isolation of microorganism that naturally produces n-3 DPA. RESULTS: In this work, we screened microorganisms in our culture collections with the goal to isolate a strain with high levels of n-3 DPA. We isolated a strain of Sphaeroforma arctica that produces up to 11% n-3 DPA in total fatty acid and has a high n-3 DPA to DHA/EPA ratio. The cell growth of the isolated strain was characterized using microscopy imaging and flow cytometer technologies to confirm the coenocytic pattern of cell divisions previously described in S. arctica. Our novel isolate of S. arctica grew more robustly and produced significantly more n-3 DPA compared to previously isolated and described strains indicating the uniqueness of the discovered strain. CONCLUSION: Overall, this work reports a first isolate n-3 DPA producing microorganism and establishes the foundation for future strain improvement and elucidation of the physiological function of this LC-PUFA for human nutrition and health.

Dietary Intakes of Long-Chain Polyunsaturated Fatty Acids and Impulsivity: Comparing Non-Restricted, Vegetarian, and Vegan Diets.

BACKGROUND: Research suggests a link between deficiencies in omega-3 long-chain polyunsaturated fatty acids (LCPUFAs) and impulsivity among psychiatric populations. However, this association is less evident in non-clinical populations. As omega-3 LCPUFAs are predominantly sourced through fish consumption, non-fish dieters may be more vulnerable to higher impulsivity. METHODS: This cross-sectional observational study explored the association between lower intakes of omega-3 LCPUFA food sources and higher self-reported measures of impulsivity among healthy adults consuming non-restricted, vegetarian, and vegan diets. RESULTS: The results from the validated Food Frequency Questionnaire showed significantly lower estimated omega-3 LCPUFA intakes among vegans and vegetarians when compared with people consuming non-restricted diets. Furthermore, although all groups scored within the normal range of impulsivity measures, vegans scored comparatively higher. Vegans also scored significantly higher in impulsivity control relating to attention than those consuming non-restricted diets. CONCLUSIONS: The significantly lower omega-3 LCPUFA dietary intakes in the vegan diets were associated with higher scores in the second-order attentional aspect of self-reported impulsiveness.

Optimal omegas - barriers and novel methods to narrow omega-3 gaps. A narrative review.

Dietary intakes of omega-3 long chain polyunsaturated fatty acids (O3LC-PUFAs) such as eicosapentaenoic and docosahexaenoic acid are central to development and health across the life course. O3LC-PUFAs have been linked to neurological development, maternal and child health and the etiology of certain non-communicable diseases including age-related cognitive decline, cardiovascular disease, and diabetes. However, dietary inadequacies exist in the United Kingdom and on a wider global scale. One predominant dietary source of O3LC-PUFAs is fish and fish oils. However, growing concerns about overfishing, oceanic contaminants such as dioxins and microplastics and the trend towards plant-based diets appear to be acting as cumulative barriers to O3LC-PUFAs from these food sources. Microalgae are an alternative provider of O3LC-PUFA-rich oils. The delivery of these into food systems is gaining interest. The present narrative review aims to discuss the present barriers to obtaining suitable levels of O3LC-PUFAs for health and wellbeing. It then discusses potential ways forward focusing on innovative delivery methods to utilize O3LC-PUFA-rich oils including the use of fortification strategies, bioengineered plants, microencapsulation, and microalgae.

The muscle regeneration marker FOXP3 is associated with muscle injury in Duchenne muscular dystrophy.

BACKGROUND: In Duchenne muscular dystrophy (DMD), the immune system cells (ISC) synthesize molecules to regulate inflammation, a process needed to regenerate muscle. The relationship between those molecules and the muscle injury is unknown. Monocytes belonging to ISC are regulated by omega-3 fatty acids (ω-3 LCPUFAs) in DMD, but whether those fatty acids influence other ISC like T-cells is unknown. OBJECTIVE: We analyzed the expression of the muscle regeneration markers (FOXP3 and AREG) in circulating leukocytes of DMD patients with different lower limb muscle functions and whether ω-3 LCPUFAs regulate the expression of those markers, and the populations of circulating T-cells, their intracellular cytokines, and disease progression (CD69 and CD49d) markers. METHODS: This placebo-controlled, double-blind, randomized study was conducted in DMD boys supplemented with ω-3 LCPUFAs (n = 18) or placebo (sunflower oil, n = 13) for six months. FOXP3 and AREG mRNA expression in leukocytes, immunophenotyping of T-cell populations, CD49d and CD69 markers, and intracellular cytokines in blood samples were analyzed at baseline and months 1, 2, 3, and 6 of supplementation. RESULTS: Patients with assisted ambulation expressed higher (P = 0.015) FOXP3 mRNA levels than ambulatory patients. The FOXP3 mRNA expression correlated (Rho = -0.526, P = 0.03) with the Vignos scale score at month six of supplementation with ω-3 LCPUFAs. CD49d + CD8 + T-cells population was lower (P = 0.037) in the ω -3 LCPUFAs group than placebo at month six of supplementation. CONCLUSION: FOXP3 is highly expressed in circulating leukocytes of DMD patients with the worst muscle function. Omega-3 LCPUFAs might modulate the synthesis of the adhesion marker CD49d + CD8 + T-cells, but their plausible impact on FOXP3 needs more research.

Long-chain polyunsaturated fatty acids influence colorectal cancer progression via the interactions between the intestinal microflora and the macrophages.

The metabolism of long-chain polyunsaturated fatty acids (LCPUFAs) is closely associated with the risk and progression of colorectal cancer (CRC). This paper aims to investigate the role of LCPUFA in the crosstalk between intestinal microflora and macrophages, as well as the effects of these three parties on the progression of CRC. The metabolism and function of LCPUFA play important roles in regulating the composition of the human gut microflora and participating in the regulation of inflammation, ultimately affecting macrophage function and polarization, which is crucial in the tumor microenvironment. The effects of LCPUFA on cellular interactions between the two species can ultimately influence the progression of CRC. In this review, we explore the molecular mechanisms and clinical applications of LCPUFA in the interactions between intestinal microflora and intestinal macrophages, as well as its significance for CRC progression. Furthermore, we reveal the role of LCPUFA in the construction of the CRC microenvironment and explore the key nodes of the interactions between intestinal flora and intestinal macrophages in the environment. It provides potential targets for the metabolic diagnosis and treatment of CRC.

Sensing and regulation of long-chain polyunsaturated fatty acids pool in marine mollusks: Characterization of UBXD8 from the razor clam Sinonovacula constricta.

The razor clam Sinonovacula constricta is known for its richness in long-chain polyunsaturated fatty acids (LC-PUFA, C ≥ 20). Previously, we demonstrated that it possesses a complete LC-PUFA biosynthetic pathway. However, the mechanisms by which it senses the LC-PUFA pool to regulate their biosynthesis remain unclear. Here, we presented the LC-PUFA sensor UBXD8 as a critical molecule in this intriguing process. The S. constricta UBXD8 (ScUBXD8) shared all characteristic features of its mammalian counterpart and exhibited high mRNA levels in digestive tissues, suggesting its functional role in this bivalve species. By purification of ScUBXD8 protein in vitro, we discovered its ability to sense unsaturated fatty acids (UFA, C ≥ 14) but not saturated ones, as evidenced by polymerization detection. Furthermore, the intensity of ScUBXD8 polymerization increased progressively with longer acyl chain lengths, greater unsaturation degrees, and higher UFA concentrations. Exceptionally, for those located at the same node in LC-PUFA biosynthetic pathway, ScUBXD8 displayed a stronger sensitivity to n-6 UFA compared to n-3 UFA. These results suggested a critical role for ScUBXD8 in balancing fatty acids composition and ratio of n-6/n-3 UFA in S. constricta. Moreover, the UAS domain was confirmed essential for ScUBXD8 polymerization. Through knockdown of ScUbxd8 gene in vivo, there were significant shifts in expression patterns of genes related to LC-PUFA biosynthesis, concurrently influencing fatty acids compositions. These results suggested that ScUBXD8 likely plays a regulatory role in LC-PUFA biosynthesis, possibly through the INSIG-SREBP pathway. Collectively, this study proposed that S. constricta might maintain LC-PUFA homeostasis through UBXD8 to regulate their biosynthesis.

Impact of Climate Change on Dietary Nutritional Quality and Implications for Asthma and Allergy.

Asthma and allergic disorders are common in childhood with genetic and environmental determinants of disease that include prenatal nutritional exposures such as long-chain polyunsaturated fatty acids and antioxidants. Global climate change is implicated in asthma and allergic disorder morbidity with potential mechanisms including perturbations of ecosystems. There is support that environmental and climatic changes such as increasing global temperate and carbon dioxide levels affect aquatic and agricultural ecosystems with subsequent alterations in long-chain polyunsaturated fatty acid availability and nutrient quality and antioxidant capacity of certain crops, respectively. This article discusses asthma epidemiology and the influence of global climate change.

Novel Approaches for Elongation of Fish Oils into Very-Long-Chain Polyunsaturated Fatty Acids and Their Enzymatic Interesterification into Glycerolipids.

Elongation of the Very-Long-Chain Fatty Acids-4 (ELOVL4) enzyme that is expressed in neuronal tissues, sperm, and testes mediates biosynthesis of very-long-chain polyunsaturated fatty acids (VLC-PUFAs) from dietary long chain PUFAs (LC-PUFAs). The VLC-PUFAs are critical for neuronal and reproductive function. Therefore, mutations in ELOVL4 that affect VLC-PUFA biosynthesis contribute to retinal degenerative diseases including Autosomal Dominant Stargardt-like Macular Dystrophy (STGD3). Recent studies have also shown not only a depletion of retinal VLC-PUFAs with normal aging but also a more significant loss of VLC-PUFAs in donor eyes of patients with age-related macular degeneration (AMD). However, currently, there are no natural sources of VLC-PUFAs to be evaluated as dietary supplements for the attenuation of retinal degeneration in animal models of STGD3. Here, we report the development of a novel chemical approach for elongation of eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids from fish oils by 6 carbon atoms to make a unique group of VLC-PUFAs, namely all-cis-hexacosa-11,14,17,20,23-pentaenoic acids (C26:5 n-3) and all-cis-octacosa-10,13,16,19,22,25-hexaenoic acids (C28:6 n-3). The three-step elongation approach that we report herein resulted in a good overall yield of up to 20.2%. This more sustainable approach also resulted in improved functional group compatibility and minimal impact on the geometrical integrity of the all-cis double bond system of the VLC-PUFAs. In addition, we also successfully used commercial deep-sea fish oil concentrate as an inexpensive material for the C6 elongation of fish oil LC-PUFAs into VLC-PUFAs, which resulted in the making of gram scales of VLC-PUFAs with an even higher isolation yield of 31.0%. The quality of fish oils and the content of oxidized lipids were key since both strongly affected the activity of the PEPPSI-IPr catalyst and ultimately the yield of coupling reactions. Downstream enzymatic interesterification was used for the first time to prepare structured glycerolipids enriched with VLC-PUFAs that could be evaluated in vivo to determine absorption and transport to target tissues relative to those of the free fatty acid forms. It turned out that in the synthesis of structured triacylglycerols and glycerophospholipids with VLC-PUFAs, the polarity of the immobilized lipase carrier and its humidity were essential.

A novel quantification method for retinal pigment epithelium phagocytosis using a very-long-chain polyunsaturated fatty acids-based strategy.

Introduction: The vertebrate retinal pigment epithelium (RPE) lies adjacent to the photoreceptors and is responsible for the engulfment and degradation of shed photoreceptor outer segment fragments (POS) through receptor-mediated phagocytosis. Phagocytosis of POS is critical for maintaining photoreceptor function and is a key indicator of RPE functionality. Popular established methods to assess RPE phagocytosis rely mainly on quantifying POS proteins, especially their most abundant protein rhodopsin, or on fluorescent dye conjugation of bulk, unspecified POS components. While these approaches are practical and quantitative, they fail to assess the fate of POS lipids, which make up about 50% of POS by dry weight and whose processing is essential for life-long functionality of RPE and retina. Methods: We have developed a novel very-long-chain polyunsaturated fatty acids (VLC-PUFA)-based approach for evaluating RPE phagocytic activity by primary bovine and rat RPE and the human ARPE-19 cell line and validated its results using traditional methods. Results and discussion: This new approach can be used to detect in vitro the dynamic process of phagocytosis at varying POS concentrations and incubation times and offers a robust, unbiased, and reproducible assay that will have utility in studies of POS lipid processing.

Urinary Metabolite Profiling to Non-Invasively Monitor the Omega-3 Index: An Exploratory Secondary Analysis of a Randomized Clinical Trial in Young Adults.

The Omega-3 Index (O3I) reflects eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content in erythrocytes. While the O3I is associated with numerous health outcomes, its widespread use is limited. We investigated whether urinary metabolites could be used to non-invasively monitor the O3I in an exploratory analysis of a previous placebo-controlled, parallel arm randomized clinical trial in males and females (n = 88) who consumed either ~3 g/d olive oil (OO; control), EPA, or DHA for 12 weeks. Fasted blood and first-void urine samples were collected at baseline and following supplementation, and they were analyzed via gas chromatography and multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS), respectively. We tentatively identified S-carboxypropylcysteamine (CPCA) as a novel urinary biomarker reflecting O3I status, which increased following both EPA and DHA (p < 0.001), but not OO supplementation, and was positively correlated to the O3I (R = 0.30, p < 0.001). Additionally, an unknown dianion increased following DHA supplementation, but not EPA or OO. In ROC curve analyses, CPCA outperformed all other urinary metabolites in distinguishing both between OO and EPA or DHA supplementation groups (AUC > 80.0%), whereas the unknown dianion performed best in discriminating OO from DHA alone (AUC = 93.6%). Candidate urinary biomarkers of the O3I were identified that lay the foundation for a non-invasive assessment of omega-3 status.

Lipidomic studies reveal two specific circulating phosphatidylcholines as surrogate biomarkers of the omega-3 index.

Optimal dietary intake of omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) is critical to human health across the lifespan. However, omega-3 index (O3I) determination is not routinely assessed due to complicated procedures for n3-LCPUFA analysis from the phospholipid (PL) fraction of erythrocytes. Herein, a high-throughput method for lipidomics based on multisegment injection-nonaqueous capillary electrophoresis-mass spectrometry was applied to identify circulating PLs as surrogate biomarkers of O3I in two randomized placebo-controlled trials. An untargeted lipidomic data workflow using a subgroup analysis of serum extracts from sunflower oil versus high-dose fish oil (FO)-supplemented participants revealed that ingested n3-LCPUFAs were primarily distributed as their phosphatidylcholines (PCs) relative to other PL classes. In both high-dose FO (5.0 g/day) and EPA-only trials (3.0 g/day), PC (16:0_20:5) was the most responsive PL, whereas PC (16:0_22:6) was selective to DHA-only supplementation. We also demonstrated that the sum concentration of both these PCs in fasting serum or plasma samples was positively correlated to the O3I following FO (r = 0.708, P = 1.02 × 10-11, n = 69) and EPA- or DHA-only supplementation (r = 0.768, P = 1.01 × 10-33, n = 167). Overall, DHA was more effective in improving the O3I (ΔO3I = 4.90 ± 1.33%) compared to EPA (ΔO3I = 2.99 ± 1.19%) in young Canadian adults who had a poor nutritional status with an O3I (3.50 ± 0.68%) at baseline. Our method enables the rapid assessment of the O3I by directly measuring two circulating PC species in small volumes of blood, which may facilitate screening applications for population and precision health.