Long-chain Polyunsaturated Fatty Acids Research Articles

Quantitative genetic analysis indicate non-heritability of major fatty acid in the muscle of Chinese mitten crab (Eriocheir sinensis)

The Chinese mitten crab (Eriocheir sinensis) is a commercially important aquaculture species, and crab meat generally has the high percentage of long-chain polyunsaturated fatty acids (LC-PUFAs) in the total fatty acids, which contributes the unique flavor and high nutrition value for adult crab. Muscle is the largest edible tissue in crustaceans, containing a variety of fatty acids, and understanding the genetic parameters of fatty acids in the meat of E. sinensis would be useful for the aquaculture of this species. This study investigated the heritability, genetic and phenotypic correlations of major fatty acids in the muscle of E. sinensis. Progeny from 25 full-sib families were reared under a common environment until they reached market size, and 429 mature crabs were selected for analysis. The results showed that the heritabilities of most fatty acids were low ranged from 0.01 (n-3PUFA) to 0.21 (MUFA), but the high heritabilities were recorded for C20:3n3 and C20:3n6 with values of 0.99 and 0.32, respectively. Furthermore, the strongest positive genetic correlations were found between C20:5n3 and C22:6n3(0.99), n-3PUFA(0.99), and PUFA and LC- PUFAs (0.99), n-3PUFA(0.99), whereas the strongest phenotype correlation was found between C20:5n3 and n-3 PUFA (0.96); C20:3n6 showed a significant negative genetic correlation with C20:3n3(−0.86) and C18:0 (−0.98), whereas C20:3n6 showed significant negative phenotypic correlation with C20:3n3(−0.14), C20:5n3(−0.15) and C22:6n3(−0.18). In conclusion, the percentages of major fatty acids, particularly C20:5n3, C22: 5n3 and C20:4n6, in E. sinensis muscle have very low heritabilities, suggesting that these fatty acids contents/composition in the muscle are ineffective targets for the selective breeding programs of E. sinensis.

A co-ordinated transcriptional programme in the maternal liver supplies long chain polyunsaturated fatty acids to the conceptus using phospholipids

The long and very long chain polyunsaturated fatty acids (LC-PUFAs) are preferentially transported by the mother to the fetus. Failure to supply LC-PUFAs is strongly linked with stillbirth, fetal growth restriction, and impaired neurodevelopmental outcomes. However, dietary supplementation during pregnancy is unable to simply reverse these outcomes, suggesting imperfectly understood interactions between dietary fatty acid intake and the molecular mechanisms of maternal supply. Here we employ a comprehensive approach combining untargeted and targeted lipidomics with transcriptional profiling of maternal and fetal tissues in mouse pregnancy. Comparison of wild-type mice with genetic models of impaired lipid metabolism allows us to describe maternal hepatic adaptations required to provide LC-PUFAs to the developing fetus. A late pregnancy-specific, selective activation of the Liver X Receptor signalling pathway dramatically increases maternal supply of LC-PUFAs within circulating phospholipids. Crucially, genetic ablation of this pathway in the mother reduces LC-PUFA accumulation by the fetus, specifically of docosahexaenoic acid (DHA), a critical nutrient for brain development.

Association between a combination of cognitively stimulating leisure activities and long-chain polyunsaturated fatty acid intake on cognitive decline among community-dwelling older Japanese individuals.

Multifactorial lifestyle approaches could be more effective than a single factor for maintaining cognitive function. This study investigated the association of combining cognitively stimulating leisure activities (CSLAs), including puzzles, quizzes, and cognitive training games, with intake of long-chain polyunsaturated fatty acids (LCPUFAs), including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA), on cognitive function in the older Japanese individuals without dementia. Participants were community-dwelling Japanese individuals without a self-reported history of dementia (n = 906, aged 60-88 years) from datasets of a 2-year longitudinal study (baseline: 2006-2008 and follow-up: 2008-2010). CSLA engagement and LCPUFA intake were divided into high and low groups according to frequency (≥once/week and <once/week) for CSLA engagement and median intake level for LCPUFA intake according to sex, then categorized into four groups. The associations of multivariate-adjusted odds ratio (OR) for a cognitive decline, shown as a decrease in the Mini-Mental State Examination score by 2 or more points, and the combination of CSLA engagement with LCPUFA intake were assessed using a multiple logistic regression model. Subgroup analysis involved participants with low DHA and EPA intakes (n = 303; median intake, 325 mg/day), mirroring those in North America. The HIGH-CSLA/HIGH-ARA group cumulatively yielded a lower OR for cognitive decline (0.41; 95% confidence interval, 0.25-0.70) than did the LOW-CSLA/LOW-ARA group (p for trend = 0.001). In the subgroup analysis, the OR for the HIGH-CSLA/HIGH-DHA group was notably reduced (0.31; 95% confidence interval, 0.11-0.87; p for trend = 0.025) compared with the LOW-CSLA/LOW-DHA group. High CSLA engagement frequency combined with high ARA intake may cumulatively reduce the risk of cognitive decline among older Japanese individuals. Furthermore, combining CSLA engagement frequency with DHA intake could have a positive association with maintaining cognitive function among older individuals, particularly those with low DHA and EPA intakes.

Marine Bioactive Compounds with Functional Role in Immunity and Food Allergy.

Food allergy, referred to as the atypical physiological overreaction of the immune system after exposure to specific food components, is considered one of the major concerns in food safety. The prevalence of this emerging worldwide problem has been increasing during the last decades, especially in industrialized countries, being estimated to affect 6-8% of young children and about 2-4% of adults. Marine organisms are an important source of bioactive substances with the potential to functionally improve the immune system, reduce food allergy sensitization and development, and even have an anti-allergic action in food allergy. The present investigation aims to be a comprehensive report of marine bioactive compounds with verified actions to improve food allergy and identified mechanisms of actions rather than be an exhaustive compilation of all investigations searching beneficial effects of marine compounds in FA. Particularly, this research highlights the capacity of bioactive components extracted from marine microbial, animal, algae, and microalgae sources, such as n-3 long-chain polyunsaturated fatty acids (LC-PUFA), polysaccharide, oligosaccharide, chondroitin, vitamin D, peptides, pigments, and polyphenols, to regulate the immune system, epigenetic regulation, inflammation, and gut dysbiosis that are essential factors in the sensitization and effector phases of food allergy. In conclusion, the marine ecosystem is an excellent source to provide foods with the capacity to improve the hypersensitivity induced against specific food allergens and also bioactive compounds with a potential pharmacological aptitude to be applied as anti-allergenic in food allergy.

Effective complete replacement of fish oil by linseed oil in diets for thick-lipped grey mullet (Chelon labrosus) juveniles reared at three environmental salinities

One of the major challenges for fish oil replacement by alternative oils is the limited capacity of marine fish species to convert 18C fatty acids into long-chain poly unsaturated fatty acids (LC-PUFA). Since salinity markedly affects this conversion capacity, euryhaline species, such as thick-lipped grey mullet (Chelon labrosus), may have a good potential to use diets without inclusion of fish oil. To test this hypothesis, thick-lipped grey mullet juveniles were fed two different diets based on fish oil (FO diet) or linseed oil (LO diet) at three different salinities: 46 ppt, 35 ppt, and 16 ppt. At the end of the trial, the biochemical and fatty acid composition of whole-body, liver, and muscle, as well as the relative expression of the genes codifying for the elongase Elovl5 and the desaturase Fads2 in liver, were determined. The results showed the good capacity of mullet juveniles to convert 18C fatty acids into LC-PUFA, which was enhanced by the replacement of FO by LO and the reduction of salinity to an isosmotic level (16 ppt). Besides, these juveniles efficiently used diets with complete replacement of FO by LO with growth performance, body composition, and LC-PUFA fatty acid profiles similar to those of fish fed FO, particularly when reared at 16 ppt.

Dissection of the synthesis of polyunsaturated fatty acids in nematodes and Collembola of the soil fauna

It is becoming increasingly clear that not only unicellular, photoautotrophic eukaryotes, plants, and fungi, but also invertebrates are capable of synthesizing ω3 long-chain polyunsaturated fatty acids (LC-PUFA) de novo. However, the distribution of this anabolic capacity among different invertebrate groups and its implementation at the gene and protein level are often still unknown. This study investigated the PUFA pathways in common soil fauna, i.e. two nematode and two Collembola species. Of these, one species each (Panagrellus redivivus, Folsomia candida) was assumed to produce ω3 LC-PUFA de novo, while the others (Acrobeloides bodenheimeri, Isotoma caerulea) were supposed to be unable to do so. A highly labeled oleic acid (99 % 13C) was supplemented and the isotopic signal was used to trace its metabolic path. All species followed the main pathway of lipid biosynthesis. However, in A. bodenheimeri this terminated at arachidonic acid (ω6 PUFA), whereas the other three species continued the pathway to eicosapentaenoic acid (ω3 PUFA), including I. caerulea. For the nematode P. redivivus the identification and functional characterization of four new fatty acid desaturase (FAD) genes was performed. These genes encode the FAD activities Δ9, Δ6, and Δ5, respectively. Additionally, the Δ12 desaturase was analyzed, yet the observed activity of an ω3 FAD could not be attributed to a coding gene. In the Collembola F. candida, 11 potential first desaturases (Δ9) and 13 front-end desaturases (Δ6 or Δ5 FADs) have been found. Further sequence analysis indicates the presence of omega FADs, specifically Δ12, which are likely derived from Δ9 FADs.

Evaluation of cottonseed oil as a substitute for fish oil in the commercial diet for juvenile swimming crab (Portunus trituberculatus)

A six-week feeding trial was carried out to determine the feasibility of cottonseed oil (CSO) as a viable substitute for fish oil (FO) in the commercial diet of swimming crab. Ninety healthy swimming crabs (initial body weight 34.28 ± 0.59 g) were randomly assigned to 90 plastic baskets. Three isonitrogenous and isolipidic diets (450 g/kg protein and 120 g/kg lipid) were formulated replacing FO with CSO at 0%, 50% and 100% (CSO-0, CSO-50, and CSO-100), respectively. Each diet was randomly allocated to three replicates, each consisting of 10 crabs. Results indicated that crabs fed with CSO-100 diet had the lowest the percent weight gain (PWG), specific growth rate (SGR) and survival among all treatments (P < 0.05). Albumin (ALB), alkaline phosphatase (ALP), glucose (GLU), triglyceride (TAG), total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), non-esterified fatty acid (NEFA) contents and alanine amino transferase (ALT) activity in hemolymph were significantly affected by dietary substitution of FO with CSO (P < 0.05). The contents of total saturated fatty acids (SFA), total mono-unsaturated fatty acids (MUFA) and total long-chain polyunsaturated fatty acids (LC-PUFA) in the hepatopancreas and muscle were negatively correlated with the substitution level, whereas total n-6 polyunsaturated fatty acids (n-6 PUFA) and linoleic acid (18:2n-6) contents increased significantly with increasing levels of dietary substitution of FO with CSO (P < 0.05). Dietary substitution of FO with CSO resulted in changes in the composition of volatile substances in muscle, with 16 volatile substances in muscle significantly affected (P < 0.05). The relative expression of genes related to lipid synthesis such as fatty acid synthase (fas), acetyl-CoA carboxylase (acc) and glycerol-3-phosphate acyltransferase 1 (gpat1) in the hepatopancreas were significantly up-regulated in the CSO-50 group compared to other treatment groups (P < 0.05). The relative expression of fatty acid anabolism-related genes fatty acyl desaturase 2 (fads2) and elongase 4 (elovl4) were significantly down-regulated with the increase of dietary substitution of FO with CSO (P < 0.05). In conclusion, 50% substitution with CSO had no negative effects on growth performance, promoted lipid synthesis and metabolism, facilitated lipid accumulation. However, complete substitution of FO with CSO inhibited fatty acid synthesis and metabolism, resulting in a lower tissue LC-PUFA content and an altered composition of muscle volatiles.

Short-term dietary changes are reflected in the cerebral content of adult ring-billed gulls.

Omega-3 long-chain polyunsaturated fatty acids (n3-LCPUFAs) are produced primarily in aquatic ecosystems and are considered essential nutrients for predators given their structural role in vertebrates' cerebral tissues. Alarmingly, with urbanization, many aquatic animals now rely on anthropogenic foods lacking n3-LCPUFAs. In this study undertaken in Newfoundland (Canada), we tested whether recent or longer term diet explains the cerebral fatty acid composition of ring-billed gulls (Larus delawarensis), a seabird that now thrives in cities. During the breeding season, cerebral levels of n3-LCPUFAs were significantly higher for gulls nesting in a natural habitat and foraging on marine food (mean ± s.d.: 32 ± 1% of total identified fatty acids) than for urban nesters exploiting rubbish (27 ± 1%). Stable isotope analysis of blood and feathers showed that urban and natural nesters shared similar diets in autumn and winter, suggesting that the difference in cerebral n3-LCPUFAs during the breeding season was owing to concomitant and transient differences in diet. We also experimentally manipulated gulls' diets throughout incubation by supplementing them with fish oil rich in n3-LCPUFAs, a caloric control lacking n3-LCPUFAs, or nothing, and found evidence that fish oil increased urban nesters' cerebral n3-LCPUFAs. These complementary analyses provide evidence that the brain of this seabird remains plastic during adulthood and responds to short-term dietary changes.

Immobilized Burkholderia cepacia lipase and its application in selective enrichment of EPA by hydrolysis of fish oil

Eicosapentaenoic acid (EPA), an orally active Omega-3 long-chain polyunsaturated fatty acid, has attracted much attention for its medical and healthcare value. Due to a large amount of polyunsaturated fatty acids (PUFA) including docosahexanoic acid (DHA) in fish oil, the highly specific enrichment of EPA from fish oil is difficult to achieve. In our study, we conducted immobilization studies on Burkholderia cepacia lipase (BCL) and its application in the selective enrichment of EPA in fish oil. BCL was immobilized on resin LX201A by covalent crosslinking, and immobilization conditions including glutaraldehyde concentration, pH, time were optimized. The optimal immobilization conditions were 0.5% glutaraldehyde, 4 h, and pH 8.0. The loading rate of BCL reached to 93.5%, and its activity was up to 68263 U/g under the optimal immobilization conditions. After hydrolysis reaction of fish oil for 15h catalyzed by immobilized BCL, EPA content showed a more increase by 33.2%, while a slight increase by 0.78% in DHA content. Moreover, after recycling use for 10 times, the catalytic efficiency of immobilized BCL remained at 93.0%. These indicated that immobilized BCL possessed good selectivity, reusability and stability, providing great application potential in EPA selective enrichment in fish oil industry.

Evaluating the Stability and Digestibility of Long-Chain Omega-3 Algal Oil Nanoemulsions Prepared with Lecithin and Tween 40 Emulsifiers Using an In Vitro Digestion Model.

The health benefits of long-chain omega-3 polyunsaturated fatty acid (LCn-3PUFA) intake have been well documented. However, currently, the consumption of oily fish (the richest dietary source of LCn-3PUFA) in the UK is far below the recommended level, and the low digestibility of LCn-3PUFA bulk oil-based supplements from triglyceride-based sources significantly impacts their bioavailability. LCn-3PUFA-rich microalgal oil offers a potential alternative for populations who do not consume oily fish, and nanoemulsions have the potential to increase LCn-3PUFA digestibility and bioavailability. The aims of this study were to produce stable algal oil-in-water nanoemulsions with ultrasonic technology to increase DHA digestibility, measured using an in vitro digestion model. A nanoemulsion of LCn-3PUFA algal oil was developed with 6% w/w emulsifiers: lecithin (LE) or an equal ratio of Tween 40 (3%) and lecithin (LTN) (3%), 50% w/w, algal oil and 44% w/w water using rotor-stator and ultrasound homogenization. The in vitro digestion experiments were conducted with a gastric and duodenal digestion model. The results showed the creation of nanoemulsions of LCn-3PUFA algal oils offers potentially significant increases in the bioavailability of DHA in the human body. The increase in digestibility can be attributed to the smaller particle size of the nanoemulsions, which allows for higher absorption in the digestive system. This showed that the creation of nanoemulsions of LCn-3PUFA algal oils offers a potentially significant increase in the bioavailability of DHA in the human body. The LE and LTN nanoemulsions had average droplet sizes of 0.340 ± 0.00 µm and 0.267 ± 0.00 µm, respectively, but the algal oil mix (sample created with same the components as the LTN nanoemulsion, hand mixed, not processed by rotor-stator and ultrasound homogenization) had an average droplet size of 73.6 ± 6.98 µm. The LTN algal oil nanoemulsion was stable in the gastric and duodenal phases without detectable destabilization; however, the LE nanoemulsion showed signs of oil phase separation in the gastric phase. Under the same conditions, the amount of DHA digested from the LTN nanoemulsion was 47.34 ± 3.14 mg/g, compared to 16.53 ± 0.45 mg/g from the algal oil mix, showing DHA digestibility from the LTN nanoemulsion was 2.86 times higher. The findings of this study contribute to the insight of in vitro DHA digestion under different conditions. The stability of the LTN nanoemulsion throughout digestion suggests it could be a promising delivery system for LCn-3PUFAs, such as DHA, in various food and pharmaceutical applications.

How Membrane Phospholipids Containing Long-Chain Polyunsaturated Fatty Acids and Their Oxidation Products Orchestrate Lipid Raft Dynamics to Control Inflammation

BackgroundLong-chain PUFA (LC-PUFA) influence varying aspects of inflammation. One mechanism by which they regulate inflammation is by controlling the size and molecular composition of lipid rafts. Lipid rafts are sphingolipid/cholesterol-enriched plasma membrane microdomains that compartmentalize signaling proteins and thereby control downstream inflammatory gene expression and cytokine production. ObjectivesThis review summarizes developments in our understanding of how LC-PUFA acyl chains of phospholipids, in addition to oxidized derivatives of LC-PUFAs such as oxidized 1-palmitoyl-2-arachidonyl-phosphatidylcholine (oxPAPC), manipulate formation of lipid rafts and thereby inflammation. MethodsWe reviewed the literature, largely from the past 2 decades, on the impact of LC-PUFA acyl chains and oxidized products of LC-PUFAs on lipid raft biophysical organization of myeloid and lymphoid cells. The majority of the studies are based on rodent or cellular experiments with supporting mechanistic studies using biomimetic membranes and molecular dynamic simulations. These studies have focused largely on the LC-PUFA docosahexaenoic acid, with some studies addressing eicosapentaenoic acid. A few studies have investigated the role of oxidized phospholipids on rafts. ResultsThe biophysical literature suggests a model in which n-3 LC-PUFAs, in addition to oxPAPC, localize predominately to nonraft regions and impart a disordering effect in this environment. Rafts become larger because of the ensuing increase in the difference in order between raft and nonrafts. Biochemical studies suggest that some n-3 LC-PUFAs can be found within rafts. This deviation from homeostasis is a potential trigger for controlling aspects of innate and adaptive immunity. ConclusionOverall, select LC-PUFA acyl chains and oxidized acyl chains of phospholipids control lipid raft dynamics and downstream inflammation. Gaps in knowledge remain, particularly on underlying molecular mechanisms by which plasma membrane receptor organization is controlled in response to oxidized LC-PUFA acyl chains of membrane phospholipids. Validation in humans is also an area for future study.

Regular Consumption of Fortified Growing-up Milk Attenuates Upper Respiratory Tract Infection among Young Children in Indonesia: A Retrospective Cohort Study

Introduction A Growing-up Milk (GUM) supplemented with short-chain Galacto-oligosaccharides (scGOS), long-chain Fructo-oligosaccharides (lcFOS), and omega-3 Long-chain Polyunsaturated Fatty Acids (n-3 LCPUFAs) could support the development of the immune system to prevent the Upper Respiratory Tract Infection (URTI) and associated morbidities. It is of interest to assess whether a daily consumption of scGOS/lcFOS/n-3 LCPUFAs-fortified GUM for a minimum of 6 months reduces URTI incidences within the subsequent 3 months among young children in Indonesia. Methods A total of 154 children aged 18 to 36 months were recruited in this retrospective cohort study and categorized into exposed and non-exposed groups (78 and 76 children, respectively). A guided interview was conducted with each subject’s parent. Demographic and clinical information was collected, including incidence of URTI within the past three months, duration of URTI, as well as the frequency of medical visits when contracting URTI. The bivariate analysis via chi-square test as well as the multivariate analysis via binary logistic regression were performed. Results The overall characteristics were similar between groups with certain distinctions. The bivariate analysis indicated the exposed group to have better protection against URTI within the past 3 months as compared to the non-exposed group (RR=0.62; 95% CI=0.41-0.92; P&lt;0.05). The multivariate analysis reinforced the finding by reporting that the exposed group was indeed protected against URTI (adjusted RR=0.42; 95% CI=0.21-0.85; P&lt;0.05). Conclusion A routine consumption of scGOS/lcFOS/n-3 LCPUFAs-fortified GUM for a minimum of 6 months among Indonesian young children protected against URTI up to 58%, suggesting that fortified GUM consumption supports proper development of the immune system.

The bioconversion of dietary α-linolenic acid to eicosapentaenoic acid in Bombyx mori

n-3 Long-chain polyunsaturated fatty acids (n-3 LC-PUFAs), including eicosapentaenoic acid (EPA), are essential multifunctional nutrients in animals. Microorganisms such as microalgae are known to be n-3 LC-PUFA producers in aquatic environments. Various aquatic invertebrates, including Harpacticoida copepods, and a few terrestrial invertebrates, such as the nematode Caenorhabditis elegans, possess n-3 LC-PUFA biosynthetic enzymes. However, the capacity for n-3 LC-PUFA biosynthesis and the underlying molecular mechanisms in terrestrial insects are largely unclear. In this study, we investigated the fatty acid biosynthetic pathway in the silkworm Bombyx mori and found that EPA was present in silkworms throughout their development. Stable isotope tracing revealed that dietary α-linolenic acid (ALA) was metabolized to EPA in silkworm larvae. These results indicated that silkworms synthesize EPA from ALA. Given that EPA is enriched in the central nervous system, we propose that EPA confers optimal neuronal functions, similar to docosahexaenoic acid, in the mammalian nervous system.

Bayesian Meta-Analysis: Impacts of Eating Habits and Habitats on Omega-3 Long-Chain Polyunsaturated Fatty Acid Composition and Growth in Cultured Fish.

Omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) such as eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) offer protective benefits against various pathological conditions, including atherosclerosis, obesity, inflammation, and autoimmune diseases. Marine fish and seafood are the primary sources of n-3 LC-PUFAs in the human diet. However, the inclusion of fish oil in aquafeeds is declining due to limited availability, fluctuating prices, sustainability concerns, and replacement with vegetable oils. While comprehensive narrative reviews on the impact of substituting fish oil with vegetable oil in aquafeeds exist, quantitative studies are relatively scarce and mainly focused on comparing the source of vegetable oils. Herein, we employed, for the first time, a Bayesian meta-analysis approach, collecting research data from 81 articles to quantitatively analyze the effects of dietary n-3 LC-PUFA levels on the n-3 LC-PUFA composition and growth performance in cultured fish. Our findings indicate that with the exception of herbivorous fish, dietary n-3 LC-PUFA levels significantly affect the EPA and DHA levels in the livers and muscles of carnivorous, omnivorous, freshwater, and marine fish. Additionally, the growths of freshwater and herbivorous fish were less affected by changes in dietary n-3 LC-PUFA levels compared to that of carnivorous and marine fish.

Subsidies of long-chain polyunsaturated fatty acids, not energy subsidies, strengthen immune responses in a terrestrial predator

Subsidies of long-chain polyunsaturated fatty acids, not energy subsidies, strengthen immune responses in a terrestrial predator

Dietary LPC-Bound n-3 LCPUFA Protects against Neonatal Brain Injury in Mice but Does Not Enhance Stem Cell Therapy.

Neonatal hypoxic-ischemic (HI) brain injury is a prominent cause of neurological morbidity, urging the development of novel therapies. Interventions with n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) and mesenchymal stem cells (MSCs) provide neuroprotection and neuroregeneration in neonatal HI animal models. While lysophosphatidylcholine (LPC)-bound n-3 LCPUFAs enhance brain incorporation, their effect on HI brain injury remains unstudied. This study investigates the efficacy of oral LPC-n-3 LCPUFAs from Lysoveta following neonatal HI in mice and explores potential additive effects in combination with MSC therapy. HI was induced in 9-day-old C57BL/6 mice and Lysoveta was orally supplemented for 7 subsequent days, with or without intranasal MSCs at 3 days post-HI. At 21-28 days post-HI, functional outcome was determined using cylinder rearing, novel object recognition, and open field tasks, followed by the assessment of gray (MAP2) and white (MBP) matter injury. Oral Lysoveta diminished gray and white matter injury but did not ameliorate functional deficits following HI. Lysoveta did not further enhance the therapeutic potential of MSC therapy. In vitro, Lysoveta protected SH-SY5Y neurons against oxidative stress. In conclusion, short-term oral administration of Lysoveta LPC-n-3 LCPUFAs provides neuroprotection against neonatal HI by mitigating oxidative stress injury but does not augment the efficacy of MSC therapy.

Enhancing Acetate Utilization in Phaeodactylum tricornutum through the Introduction of Acetate Transport Protein.

The diatom Phaeodactylum tricornutum, known for its high triacylglycerol (TAG) content and significant levels of n-3 long chain polyunsaturated fatty acids (LC-PUFAs), such as eicosapentaenoic acid (EPA), has a limited ability to utilize exogenous organic matter. This study investigates the enhancement of acetate utilization in P. tricornutum by introducing an exogenous acetate transport protein. The acetate transporter gene ADY2 from Saccharomyces cerevisiae endowed the organism with the capability to assimilate acetate and accelerating its growth. The transformants exhibited superior growth rates at an optimal NaAc concentration of 0.01 M, with a 1.7- to 2.0-fold increase compared to the wild-type. The analysis of pigments and photosynthetic activities demonstrated a decline in photosynthetic efficiency and maximum electron transport rate. This decline is speculated to result from the over-reduction of the electron transport components between photosystems due to acetate utilization. Furthermore, the study assessed the impact of acetate on the crude lipid content and fatty acid composition, revealing an increase in the crude lipid content and alterations in fatty acid profiles, particularly an increase in C16:1n-7 at the expense of EPA and a decrease in the unsaturation index. The findings provide insights into guiding the biomass and biologically active products production of P. tricornutum through metabolic engineering.

Targeted lipidomics uncovers oxylipin perturbations and potential circulation biomarkers in Bietti's crystalline dystrophy.

Abnormalities in lipid metabolism have been proposed in Bietti's crystalline dystrophy (BCD). We aim to characterize the lipid profiles in a case-control study. All participants were genetically confirmed by CYP4V2 gene sequencing and underwent chorioretinopathy evaluation by calculating the percentages of AF atrophy (PAFA). Fasting blood samples of BCD patients and controls were collected, and plasma was analyzed for routine lipid profiles. Targeted lipidomic evaluation includes long chain polyunsaturated fatty acids (LCPUFA) and associated eicosanoid metabolites. Routine lipids profiles showed elevated plasma levels of triglyceride (P = 0.043) and low-density lipoprotein cholesterol (P = 0.024) in BCD patients. Lipidomic analysis showed significantly decreased levels of ω-3 LCPUFA including docosahexaenoic acid (DHA, 22:6, P = 0.00068) and eicosapentaenoic acid (EPA, 20:5, P = 0.0016), as well as ω-6 LCPUFA arachidonic acid (ARA, 20:4, P < 0.0001) in BCD patients. Eicosanoid metabolites, either derived from ω-3 and/ or ω-6 LCPUFAs via cyclooxygenase (COX) or lipoxygenase (LOX) pathways, including 5-HEPE, 12-HEPE, 13-HDHA, 15-HETE, 12-HETE, 5-HETE, 6k-PGF1a, PGE2, PGJ2, and TXB2, exhibited significant differences (P < 0.0001) between BCD patients and controls. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites including 5-HETE, 5-HEPE, 12-HEPE and LTB4. BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA), as well as their downstream metabolites via the COX and LOX pathways, suggesting that these might be implicated in BCD pathogenesis and could serve as biomarkers and therapeutic targets of the disease. What is known BCD is a vision-threatening hereditary disease the causative gene of which is CYP4V2. Abnormalities in lipid metabolism have been proposed and demonstrated previously in BCD studies. The detailed pathogenesis remains unclear and controversial. What is new We observed prominent lipidomic alterations in the circulation when compared with age, gender, and bodymass index (BMI)-matched healthy controls. BCD patients demonstrated significant decreases in plasma levels of ω-3 and ω-6 LCPUFA (DHA, EPA, and ARA). Remarkable changes were observed in the downstream metabolites of the LCPUFA via the COX and LOX pathways. Genotypes of CYP4V2, specifically the biallelic null mutations, were observed to correlate with more remarkably reduced levels of oxylipins, involving major LOX pathway metabolites.

Functional Impact of the FADS1 rs174546 Single Nucleotide Polymorphism on Serum Lipid Levels: Insights from Molecular Mechanisms and Therapeutic Perspectives in Korean Population.

Single nucleotide polymorphisms (SNP) in the fatty acid desaturase 1 (FADS1) gene is suggested as risk factor of metabolic diseases in genome-wide association studies (GWAS). This study hypothesized that FADS1_rs174546T associates with serum triglycerides (TG) in Korean Genome and Epidemiology Study (KoGES). In addition, functional study of SNP genotypes in cultured cells is performed. FADS1_rs174546T is associated with high level of serum TG (effect size of variant: 6.48 ± 1.84mgdL-1) in Korean individuals (normotriglyceridemia, n = 5128; hypertriglyceridemia, n = 3714). Functional study in cells with FADS1_rs174546T, shows reduced transcriptional activity, when compared with rs174546C. MiR-6728-3p, which is predicted to bind with rs174546T, decreases transcriptional activity of rs174546T but not in rs174546C, and it is reversed by miR-6728-3p inhibitor. Formononetin is selected as binding molecule to 3'-UTR of FADS1 and increases luciferase activity in both rs174546 (C/T). Moreover, formononetin compensates for the reduced luciferase activity by rs174546T and miR-6728-3p. Formononetin also increases endogenous FADS1 expression and long-chain polyunsaturated fatty acid (LC-PUFA) ratio. FADS1_rs174546T is a crucial risk factor for hypertriglyceridemia in the Koreans potentially through the interaction with miR-6728-3p. Formononetin can be a potent dietary intervention to prevent and improve hypertriglyceridemia in both rs174546 (C/T) populations.

Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline.

The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2 C234W ) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE, HTRA1 and complement proteins in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of several variants in the human ELOVL2 locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.