Availability Of Polyunsaturated Fatty Acids Research Articles

Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer

Ferroptosis is a type of regulated cell death characterized by iron accumulation and lipid peroxidation. The molecular mechanisms underlying ferroptosis regulation in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that protein kinase A (PKA) inhibition enhanced ferroptosis susceptibility in NSCLC cells, as evidenced by reduced cell viability and increased lipid peroxidation. We further identified cAMP-responsive element protein 1 (CREB1), a transcription factor and a substrate of PKA, as a key regulator of ferroptosis. Knockdown of CREB1 sensitized NSCLC cells to ferroptosis inducers (FINs) and abolished the effects of PKA inhibitor and agonist, revealing the pivotal role of CREB1 in ferroptosis regulation. Using a high-throughput screening approach and subsequent validation by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, we discovered that CREB1 transcriptionally activated stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids. SCD conferred ferroptosis resistance by decreasing the availability of polyunsaturated fatty acids for lipid peroxidation, and its overexpression rescued the effect of CREB1 knockdown on ferroptosis in vitro. Besides, CREB1 knockdown suppressed xenograft tumor growth in the presence of Imidazole Ketone Erastin (IKE), a potent FIN, and this effect was reversed by SCD. Finally, we showed that high expression of CREB1 was associated with poor prognosis in NSCLC patients from public datasets and our institution. Collectively, this study illustrates the effect of PKA/CREB1/SCD axis in regulating ferroptosis of NSCLC, targeting this pathway may provide new strategies for treating NSCLC patients.

Mixotrophic Cultivation of Chlorella vulgaris on Banana Waste for Biodiesel Production

Environmentally friendly biofuels are currently produced in large quantities using algal lipids. Objective: To perform mixotrophic cultivation of Chlorella vulgaris on Banana Waste for Biodiesel Production. Methods: Banana waste was treated with acid/alkaline, ground, and sun dried. The resultant hydrolysate was used into studies comparing photoautotrophic and mixotrophic conditions in microalgae culture. When biomass productivity and lipid content were measured. For mono-unsaturated, poly-unsaturated, and saturated forms, the lipid content differed. The research used analytical methods for fatty acid methyl ester analysis, such as GC-MS. Results: Mixotrophic cultivation exhibited a much higher biomass productivity (135 mg L-1 d-1) than photoautotrophic cultivation (115 mg L-1 d-1). Additionally, mixotrophically raised biomass had a much larger (w/w) lipid content (45%) than photo-autotrophically raised biomass (30 %). Higher amount of polyunsaturated fatty acids (palmitic and oleic acids) was shown by Lipidome. Conclusions: High-quality biofuel might be made possible by the regular availability of polyunsaturated fatty acids (64 mg g-1 of dry biomass) in the lipid contents of mixotrophically produced algal biomass

Adverse effects of gestational ω-3 and ω-6 polyunsaturated fatty acid imbalance on the programming of fetal brain development.

Obesity is a key medical challenge of our time. The increasing number of children born to overweight or obese women is alarming. During pregnancy, the circulation of the mother and her fetus interact to maintain the uninterrupted availability of essential nutrients for fetal organ development. In doing so, the mother's dietary preference determines the amount and composition of nutrients reaching the fetus. In particular, the availability of polyunsaturated fatty acids (PUFAs), chiefly their ω-3 and ω-6 subclasses, can change when pregnant women choose a specific diet. Here, we provide a succinct overview of PUFA biochemistry, including exchange routes between ω-3 and ω-6 PUFAs, the phenotypes, and probable neurodevelopmental disease associations of offspring born to mothers consuming specific PUFAs, and their mechanistic study in experimental models to typify signaling pathways, transcriptional, and epigenetic mechanisms by which PUFAs can imprint long-lasting modifications to brain structure and function. We emphasize that the ratio, rather than the amount of individual ω-3 or ω-6 PUFAs, might underpin physiologically correct cellular differentiation programs, be these for neurons or glia, during pregnancy. Thereupon, the PUFA-driven programming of the brain is contextualized for childhood obesity, metabolic, and endocrine illnesses.

Temperature, phosphorus and species composition will all influence phytoplankton production and content of polyunsaturated fatty acids.

Temperature increases driven by climate change are expected to decrease the availability of polyunsaturated fatty acids in lakes worldwide. Nevertheless, a comprehensive understanding of the joint effects of lake trophic status, nutrient dynamics and warming on the availability of these biomolecules is lacking. Here, we conducted a laboratory experiment to study how warming (18-23°C) interacts with phosphorus (0.65-2.58μM) to affect phytoplankton growth and their production of polyunsaturated fatty acids. We included 10 species belonging to the groups diatoms, golden algae, cyanobacteria, green algae, cryptophytes and dinoflagellates. Our results show that both temperature and phosphorus will boost phytoplankton growth, especially stimulating certain cyanobacteria species (Microcystis sp.). Temperature and phosphorus had opposing effects on polyunsaturated fatty acid proportion, but responses are largely dependent on species. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) synthesizing species did not clearly support the idea that warming decreases the production or content of these essential polyunsaturated fatty acids. Our results suggest that warming may have different effects on the polyunsaturated fatty acid availability in lakes with different nutrient levels, and that different species within the same phytoplankton group can have contrasting responses to warming. Therefore, we conclude that future production of EPA and DHA is mainly determined by species composition.

Manipulating omega-3 and omega-6 fatty acids in sheep: depletion of long-chain omega-3 polyunsaturated fatty acids by feeding different grain types

Context Plasma fatty acid profiles provide evidence of short-term feeding, while red blood cells (RBC) indicate longer-term feeding effects. Information on the rate of change in fatty acid profiles of sheep blood over time after alterations in diet is lacking. This study monitored the short- and longer-term effects of feeding grain-based diets to lambs on changes to omega-3 polyunsaturated fatty acids (PUFA) in blood fractions over 21 days. The data provide a guide to managing omega-3 PUFA availability for adequate tissue accretion of these fatty acids. Aims To determine the rate of depletion over 21 days of omega-3 PUFA in the blood fractions of sheep fed on grain-based diets. Methods Blood samples were taken from ewes taken off pasture and fed grain-based diets for 21 days. Fatty acid profiles in the blood plasma and RBC were used to monitor the rate of depletion of omega-3 PUFA. Key results Immediate changes in plasma omega-3 PUFA concentrations occurred from the first day of grain feeding. The omega-3 PUFA content declined continuously on all five grains, but with substantial differences among them. RBC omega-3 PUFA contents displayed great variation across individual sheep but depletion was not significant. Conclusions Plasma omega-3 PUFA depletion immediately on grain feeding indicated a lower availability for tissue accretion in growing sheep following short-term changes in diet. The lack of change in RBC omega-3 PUFA concentrations over 21 days indicated a differential accumulation of these fatty acids in this lipid depot compared with plasma, and changes in other tissues should also be examined. Implications The effect of these short- and long-term changes on LCn-3PUFA accumulation in meat and reproductive tissues warrants further investigation.

Cross-Ecosystem Linkages: Transfer of Polyunsaturated Fatty Acids From Streams to Riparian Spiders via Emergent Insects

Polyunsaturated fatty acids (PUFAs) are essential resources unequally distributed throughout landscapes. Certain PUFAs, such as eicosapentaenoic acid (EPA), are common in aquatic but scarce in terrestrial ecosystems. In environments with low PUFA availability, meeting nutritional needs requires either adaptations in metabolism to PUFA-poor resources or selective foraging for PUFA-rich resources. Amphibiotic organisms that emerge from aquatic ecosystems represent important resources that can be exploited by predators in adjacent terrestrial habitats. Here, we traced PUFA transfer from streams to terrestrial ecosystems, considering benthic algae as the initial PUFA source, through emergent aquatic insects to riparian spiders. We combined carbon stable isotope and fatty acid analyses to follow food web linkages across the ecosystem boundary and investigated the influence of spider lifestyle (web building vs. ground dwelling), season, and ecosystem degradation on PUFA relations. Our data revealed that riparian spiders consumed considerable amounts of aquatic-derived resources. EPA represented on average 15 % of the total fatty acids in riparian spiders. Season had a strong influence on spider PUFA profiles, with highest EPA contents in spring. Isotope data revealed that web-building spiders contain more aquatic-derived carbon than ground dwelling spiders in spring, although both spider types had similarly high EPA levels. Comparing a natural with an anthropogenically degraded fluvial system revealed higher stearidonic acid (SDA) contents and Σω3/Σω6 ratios in spiders collected along the more natural river in spring but no difference in spider EPA content between systems. PUFA profiles of riparian spiders where distinct from other terrestrial organism and more closely resembled that of emergent aquatic insects (higher Σω3/Σω6 ratio). We show here that the extent to which riparian spiders draw on aquatic PUFA subsidies can vary seasonally and depends on the spider’s lifestyle, highlighting the complexity of aquatic-terrestrial linkages.

Mixotrophic cultivation of Chlorella vulgaris in sugarcane molasses preceding nitrogen starvation: Biomass productivity, lipid content, and fatty acid analyses

AbstractIn the present study, a precharacterized oleaginous microalgal species (Chlorella vulgaris) was exploited for its biomass productivity, lipid yield, and fatty acid analysis under mixotrophic and photoautotrophic conditions. For the purpose, the microalgal biomass was raised mixotrophically as well photoautotrophically. For mixotrophic cultivation, molasses was used as additional source of carbon and energy, while for photoautotrophic cultivation, atmospheric CO2 was the sole source of carbon and energy. The microalgal biomass raised thus was then harvested following 5 days of nitrogen starvation. Mixotrophic cultivation depicted remarkably higher biomass productivity (137.43 ± 13.3 mg L−1 day−1) than that of photoautotrophic cultivation (91.57 ± 7.9 mg L−1 day−1). About 39% (w/w) of total lipid content was obtained from the dried biomass raised mixotrophically. Lipidomic analysis of the extracted oil depicted higher concentrations of polyunsaturated fatty acids (palmitic and oleic acids). The significant availability of polyunsaturated fatty acids (60 mg g−1 of dried algal biomass) ensured the production of high quality biofuel.

Intrapopulation variability in a functional trait: Susceptibility ofDaphniato limitation by dietary fatty acids

AbstractFunctional traits are measurable characteristics of an organism that have an impact on its fitness. Variation in functional traits between and among species has been suggested to represent the basis for competition and selection, thus allowing for evolution in natural populations.In freshwater ecosystems, the availability of essential polyunsaturated fatty acids (PUFAs), in particular ω3‐ and ω6‐PUFAs, determines the food quality of phytoplankton for the herbivorous zooplanktonDaphnia, an unselective filter feeder. The content of such essential PUFAs in the phytoplankton is thus a functional phytoplankton trait affecting the trophic transfer efficiency and dynamics at the pelagic plant–herbivore interface.In turn, the susceptibility of consumers to become limited by the availability of essential PUFAs is a fitness‐determining trait ofDaphniagenotypes, and variability of this herbivore trait may thus affect the daphnids’ intrapopulation competition. To estimate the intrapopulation variation in susceptibility, we isolated clonal lines ofDaphnia longispinafrom a natural population and compared the strength of their limitation by dietary PUFA availability via standardised laboratory growth assays. We used a liposome supplementation technique to enrich a PUFA‐poor green alga with essential ω3‐ and ω6‐PUFAs and determined juvenile somatic growth rate of differentD. longispinagenotypes as a fitness proxy.As expected,D. longispinagenotypes that coexisted in a natural population differed markedly in their specific patterns of susceptibility to dietary PUFA availability. On average, theD. longispinapopulation was more strongly susceptible to limitations in the availability of the ω6‐PUFA arachidonic acid (20:4ω6) than to limitations in the availability of ω3‐PUFAs α‐linolenic acid (18:3ω3) and eicosapentaenoic acid (20:5ω3).The ability to cope with PUFA limitation is thus a crucial trait that can probably affect intraspecific competition andDaphniapopulation structure. Therefore, we suggest that such intrapopulation variation in susceptibility to absence of dietary PUFAs might be one of the driving forces of natural selection and local adaptation among freshwater zooplankton.

Fatty acid metabolism and modifications in Chironomus riparius.

A priori knowledge of fatty acid modifications in consumers is essential for studies using fatty acids as biomarkers. We investigated fatty acid metabolism and possible modification pathways in benthic invertebrate Chironomus riparius larvae (Diptera). We conducted diet manipulation experiments using natural food sources (two chlorophyte algae, a diatom and a non-toxic cyanobacterium). We also did a diet-switch experiment on two different resources, fish food flakes TetraMin® and cyanobacterium Spirulina, to study fatty acid turnover in Chironomus. Results of the diet manipulation experiments indicate that Chironomus larvae have a strong tendency to biosynthesize 20:5n-3 and 20:4n-6 from precursor fatty acids, and that the dietary availability of polyunsaturated fatty acids (PUFA) does not control larval growth. Fatty acid modifications explain why low dietary availability of PUFA did not significantly limit growth. This has ecologically relevant implications on the role of benthic chironomids in conveying energy to upper trophic level consumers. A diet-switch experiment showed that the turnover rate of fatty acids in Chironomus is relatively fast--a few days. The compositional differences of algal diets were large enough to separate Chironomus larvae into distinct groups even if significant modification of PUFA was observed. In summary, fatty acids are excellent dietary biomarkers for Chironomus, if modifications of PUFA are considered, and will provide high-resolution data on resource use. This article is part of the theme issue 'The next horizons for lipids as 'trophic biomarkers': evidence and significance of consumer modification of dietary fatty acids'.

Variation in ω-3 and ω-6 Polyunsaturated Fatty Acids Produced by Different Phytoplankton Taxa at Early and Late Growth Phase.

Phytoplankton synthesizes essential ω-3 and ω-6 polyunsaturated fatty acids (PUFA) for consumers in the aquatic food webs. Only certain phytoplankton taxa can synthesize eicosapentaenoic (EPA; 20:5ω3) and docosahexaenoic acid (DHA; 22:6ω3), whereas all phytoplankton taxa can synthesize shorter-chain ω-3 and ω-6 PUFA. Here, we experimentally studied how the proportion, concentration (per DW and cell-specific), and production (µg FA L−1 day−1) of ω-3 and ω-6 PUFA varied among six different phytoplankton main groups (16 freshwater strains) and between exponential and stationary growth phase. EPA and DHA concentrations, as dry weight, were similar among cryptophytes and diatoms. However, Cryptomonas erosa had two–27 times higher EPA and DHA content per cell than the other tested cryptophytes, diatoms, or golden algae. The growth was fastest with diatoms, green algae, and cyanobacteria, resulting in high production of medium chain ω-3 and ω-6 PUFA. Even though the dinoflagellate Peridinium cinctum grew slowly, the content of EPA and DHA per cell was high, resulting in a three- and 40-times higher production rate of EPA and DHA than in cryptophytes or diatoms. However, the production of EPA and DHA was 40 and three times higher in cryptophytes and diatoms than in golden algae (chrysophytes and synyrophytes), respectively. Our results show that phytoplankton taxon explains 56–84% and growth phase explains ~1% of variation in the cell-specific concentration and production of ω-3 and ω-6 PUFA, supporting understanding that certain phytoplankton taxa play major roles in the synthesis of essential fatty acids. Based on the average proportion of PUFA of dry weight during growth, we extrapolated the seasonal availability of PUFA during phytoplankton succession in a clear water lake. This extrapolation demonstrated notable seasonal and interannual variation, the availability of EPA and DHA being prominent in early and late summer, when dinoflagellates or diatoms increased.

How does polyunsaturated fatty acid biosynthesis regulate T‐lymphocyte function?

AbstractImpaired regulation of immune function characterised by chronic inflammation together with a declining protective immune response is a major challenge to healthy ageing. It is therefore important to understand the mechanisms that regulate immune function and the impact of ageing upon such processes. Appropriate induction and resolution of the immune response require adequate availability of polyunsaturated fatty acids (PUFAs) for incorporation into cell membranes. However, humans are unable to synthesise PUFAs de novo and are dependent upon dietary intake for pre‐formed PUFAs or synthesis by the liver from the essential fatty acids, linoleic acid (LA, 18:2n‐6) and alpha‐linolenic acid (aLNA, 18:3n‐3). We have shown that activation of peripheral blood mononuclear cells increases PUFA biosynthesis from essential fatty acids via a mechanism that involves altered epigenetic regulation of a key gene in the pathway. Moreover, induction of PUFA synthesis is directly involved in the regulation of lymphocyte activation and proliferation. The aim of the Biotechnology and Biological Sciences Research Council responsive mode award described in this paper, ‘How does polyunsaturated fatty acid biosynthesis regulate T‐lymphocyte function?’, is to determine how PUFA biosynthesis regulates T‐cell function and the effect of ageing on this process. The project will identify points of regulation in the biosynthetic pathway and how these might influence the capacity for up‐regulation of PUFA synthesis in older individuals. We will use stable isotope tracers of LA and aLNA to determine whether newly synthesised PUFAs are preferential substrates for synthesis of lipid mediators and whether they are involved in formation of membrane microdomains that mediate cell signalling.

Effects of Weekly Running Volume on Polyunsaturated Fatty Acid Metabolism: An Observational Study in Non-elite Marathon Runners (P08-100-19)

ObjectivesTissue availability of polyunsaturated fatty acids (PUFA) depends on several factors, including dietary intake, physical exercise, genetic variation and metabolic turnover. However, there is limited evidence whether running training activity per se may influence indices associated with PUFA metabolism such as Omega-3 (ω-3) index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio. The objective was to examine the association between kilometres (Km) run per week and changes in ω-3 Index and AA/EPA ratio. MethodsWe conducted a retrospective, observational, cohort study of 257 non-elite runners (mean age: 40.85 ± 12.17 years) who consumed no fatty acid supplements and provided a blood sample for analysis. The whole blood samples were collected by finger sticks, stored on absorbent filter paper, and then PUFA were quantified by gas chromatography (GC) and ω-3 Index and AA/EPA ratio measured. ResultsIn a multivariate linear regression model, a gradual decrease of the ω-3 Index was observed with higher weekly running distance (β = −0.528; 95% CI −0.039 to −0.026; R2 = 0.447; P < 0.0001). We also found a progressive increase of the AA/EPA ratio in subjects who ran greater weekly distances (β = −0.341; 95% CI −0.071 to −0.038; R2 = 0.320; P = 0.001). No other significant associations were observed with other variables, including years of running training and weekly training frequency (hours/week). Finally, as expected, a significant inverse correlation between ω-3 Index and AA/EPA ratio (β = −0419; 95% CI −3.407 to −1.821; R2 = 0.336; P < 0.0001) was detected. ConclusionsThese findings suggest that distance running training and its weekly volume may negatively contribute to changes of the ω-3 Index and AA/EPA ratio. Further studies with greater sample size will be required to replicate and extend these data. Funding SourcesThis work was supported, in part, by a grant from “Fondazione Paolo Sorbini per la scienza nell’alimentazione”. Supporting Tables, Images and/or Graphs▪▪▪▪

Effect of ocean acidification on the nutritional quality of marine phytoplankton for copepod reproduction.

Phytoplankton are the oceans’ principal source of polyunsaturated fatty acids that support the growth and reproduction of consumers such as copepods. Previous studies have demonstrated ocean acidification (OA) can change the availability of polyunsaturated fatty acids to consumer diets which may affect consumer reproduction. Two laboratory experiments were conducted to examine the effects of feeding high-pCO2-reared phytoplankton on copepod egg production, hatching success, and naupliar survival. Marine phytoplankton Rhodomonas salina, Skeletonema marinoi, Prorocentrum micans, and Isochrysis galbana were exponentially grown in semi-continuous cultures at present (control) (400 ppm CO2, pH~8.1) and future (1,000 ppm CO2, pH~7.8) conditions and provided to Acartia tonsa copepods over 4 consecutive days as either nitrogen-limited (Exp. I) or nitrogen-depleted (Exp. II) mixed assemblage of phytoplankton. The composition of FAs in the phytoplankton diet was affected by pCO2 concentration and nitrogen deficiency; the ratio of essential fatty acids to total polyunsaturated fatty acids decreased in phytoplankton grown under high pCO2 and the mass of total fatty acids increased under nitrogen depletion. Additionally, total concentrations of essential fatty acids and polyunsaturated fatty acids in the diet mixtures were less under the high-pCO2 compared to the control-pCO2 treatments. Median egg production, hatching success, and naupliar survival were 48–52%, 4–87%, and 9–100% lower, respectively, in females fed high-pCO2 than females fed low-pCO2 phytoplankton, but this decrease in reproductive success was less severe when fed N-depleted, but fatty acid-rich cells. This study demonstrates that the effects of OA on the nutritional quality of phytoplankton (i.e., their cellular fatty acid composition and quota) were modified by the level of nitrogen deficiency and the resulting negative reproductive response of marine primary consumers.

Relationship Between Distance Run Per Week, Omega-3 Index, and Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio: An Observational Retrospective Study in Non-elite Runners.

Background: Tissue availability of polyunsaturated fatty acids (PUFA) depends on several factors, including dietary intake, physical exercise, genetic variation, and metabolic turnover. However, there is limited evidence whether running training activity per se may influence indices associated with PUFA metabolism such as Omega-3 (ω-3) index and arachidonic acid (AA; 20:4ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio.Objective: To examine the association between kilometers (Km) run per week and changes in ω-3 index and AA/EPA ratio.Methods: We conducted a retrospective, observational, cohort study of 257 non-elite runners (mean age: 40.85 ± 12.17 years) who consumed no fatty acid supplements and provided a blood sample for analysis. The whole blood samples were collected by finger sticks, stored on absorbent filter paper, and then PUFA were quantified by gas chromatography (GC) and ω-3 index and AA/EPA ratio measured.Results: In a multivariate linear regression model, a gradual decrease of the ω-3 index was observed with higher weekly running distance (β = −0.033; 95% CI −0.039 to −0.026; R2 = 0.447; p < 0.0001). We also found a progressive increase of the AA/EPA ratio in subjects who ran greater weekly distances (β = 0.092; 95% CI 0.038 to 0.146; R2 = 0.320; p = 0.001). No other significant associations were observed with other variables, including years of running training and weekly training frequency (hours/week). Finally, as expected, a significant inverse correlation between ω-3 index and AA/EPA ratio (β = −2.614; 95% CI −3.407 to −1.821; R2 = 0.336; p < 0.0001) was detected.Conclusions: These findings suggest that distance running training and its weekly volume may negatively contribute to changes of the ω-3 index and AA/EPA ratio. Further studies with greater sample size will be required to replicate and extend these data.

PUFA supplementation may confer enhanced metabolic capacity in stimulated skeletal muscle cells

Skeletal muscle is an energetically demanding tissue that catabolizes a variety of different substrates, a phenomenon that is largely activity‐dependent. Lipids are an energetically‐rich macromolecule and, in this light, are advantageous for skeletal muscle performance and maintenance. It has long been established that lipids have dichotomous lasting effects on the body that appear to be, at least in part, species‐specific. While lipid‐related pathologies are largely associated with species such as saturated fatty acids, diacylglycerols, and ceramides, other lipid species, such as various unsaturated fatty acids, confer adaptive changes and may actually protect against diseases. Lipids have previously been linked to increased aerobic capacity in skeletal muscle, though the role of fatty acid quality in this context (e.g., degree of saturation) is less clear. In the present study, we used C2C12 cells, an immortalized line of mouse skeletal muscle cells, to better understand how polyunsaturated fatty acids (PUFAs), in combination with exercise, affect metabolism and protein concentration in skeletal muscle. Following standard proliferation protocols, mature myotubes were differentiated for 7 days in either control media or media supplemented with a 5% addition of linoleic acid (PUFA); additionally, to stimulate contractile activity, a subset of cell cohorts from each media group were exposed to caffeine for 20 minutes per day during differentiation days 4–7. All cells were harvested for protein on differentiation day seven. Protein concentration across cohorts was measured using a Bradford protein assay. Metabolic changes were characterized by running functional enzyme assays for lactate dehydrogenase (LDH) and citrate synthase (CS) to compare anaerobic and aerobic changes, respectively. Preliminary data show that non‐exercised cohorts have higher protein concentration when supplemented PUFA, and that exercise, both with and without PUFA supplementation, decreases protein concentration as compared to respective non‐exercised cohorts. Regarding enzyme activity, PUFA supplementation appears to decrease LDH activity in non‐exercised cells, while PUFA supplementation appears to increase LDH activity in exercised cells; CS activity also appears to change in PUFA supplemented cohorts. Collectively, these preliminary data suggest activity‐induced adaptive changes in skeletal muscle metabolism are contingent upon specific substrate availability, whereby PUFA availability may advantageously prime skeletal muscle for a higher overall metabolic capacity.Support or Funding InformationMcNair Scholars Program and The College of Saint ScholasticaThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The essential omega-3 fatty acid EPA affects expression of genes involved in the metabolism of omega-6-derived eicosanoids in Daphnia magna

Eicosanoids are an important class of signalling molecules derived from essential polyunsaturated fatty acids (PUFAs). Some recent research had started to investigate the eicosanoid pathway in Daphnia magna, but focussed mostly on the role of omega-6 PUFAs, rather than on the nutritionally important omega-3 PUFA eicosapentaenoic acid (EPA), which is known to determine the trophic transfer efficiency from phytoplankton to cladoceran zooplankton in freshwater foodwebs. To test for the relevance of EPA for the expression of genes in the eicosanoid pathway, we conducted highly controlled feeding experiments with D. magna under two temperature conditions and supplemented diets differing only in their EPA contents. Some, but not all genes previously reported to be related to the eicosanoid metabolism of D. magna, were significantly upregulated when EPA was available in the diet. Other genes from the eicosanoid pathway and two control genes not related to eicosanoid metabolism were unaffected by dietary EPA availability. Our data demonstrate that dietary omega-3 PUFA availability affects the expression of some genes typically considered to be part of the omega-6 PUFA-dependent eicosanoid metabolism. These findings may thus advance our understanding of the biochemical physiology of this essential dietary compound and its role for zooplankton nutrition.

T25. ALTERATIONS OF PLASMA PHOSPHOLIPID FATTY ACID PROFILES ARE ASSOCIATED WITH LOCAL BRAIN STRUCTURAL ABNORMALITIES IN NEUROLEPTIC NAïVE FIRST-EPISODE PSYCHOSIS PATIENTS

BackgroundAlterations in brain structure are among the most robust biological findings in schizophrenia. Also changes in fatty acid profiles including reduced levels of polyunsaturated fatty acids (PUFA) are well replicated in schizophrenia. Being essential for neurodevelopmental processes and structural plasticity and remodeling, alterations of PUFA metabolism might be also associated with the occurrence of brain structural abnormalities. To investigate this assumption in vivo we examined the interrelation of PUFA profiles and brain structure in neuroleptic naïve first-episode psychosis (FEP) patients and healthy controls (HC) matched for age and gender.MethodsHigh-resolution T1-weighted 3T MRI were acquired from 29 FEP patients (age 26.4 ± 5.3y; 13 females/16 males) and 31 HC (age 25.1 ± 4.7y; 14 f/17 m). Fatty acid profiles were analyzed using gas chromatography in the plasma phospholipid (PL) fraction that is rather independent of recent fat consumption, and that potentially indicates PUFA availability in phospholipid structural components essential in the brain. To investigate brain structural abnormalities in FEP and effects of illness on interactions between fatty acid profiles and local grey (GM) or white (WM) matter density, voxel-based morphometry (VBM) with the computational anatomy toolbox (CAT12) was used.ResultsVBM analyses revealed a reduction of GM in FEP in left frontal operculum, left middle frontal gyrus, left superior frontal gyrus and bilateral temporal gyrus (TFCE, FWE<0.05). The group comparisons of fatty acid profiles in the PL fraction showed reduced omega-6 PUFA and MCFA (C10-C14) levels in FEP patients. Interaction analyses revealed an influence of illness on the association between omega-6 PUFA and GM density at the left supramarginal gyrus/left postcentral gyrus and left superior temporal gyrus (TFCE, FWE<0.05) with a regression slope FEP patients > HC. For MCFA interaction analyses revealed effects of illness on associations with GM density in the bilateral superior medial frontal gyrus and left anterior cingulate gyrus with a regression slope HC > FEP patients.DiscussionOur results support the notion that the availability of PUFA and MCFA potentially affects brain structural development and remodeling. They also support the notion of PUFA and phospholipids metabolism as a biochemical basis to create early prevention and intervention strategies, e.g. by PUFA supplementation.

Supplementation of linoleic acid (C18:2n-6) or α-linolenic acid (C18:3n-3) changes microbial agonist-induced oxylipid biosynthesis

Oxylipids are derived from polyunsaturated fatty acids (PUFA) in cellular membranes and the relative abundance or balance may contribute to disease pathogenesis. Previous studies documented unique oxylipid profiles from cows with either coliform or Streptococcus uberis mastitis, suggesting that lipid mediator biosynthesis may be dependent on the type of microbial-derived agonist. Changing the fatty acid content of peripheral blood leukocytes also may be critical to the relative expression of oxylipid profiles and the outcome of bacterial infection. No information is available in dairy cows describing how changing cellular PUFA content will modify oxylipids in the context of a microbial agonist challenge. Therefore, the hypothesis for the current study was that PUFA supplementation would change bovine leukocyte fatty acid content and respective oxylipid profiles from ex vivo microbial agonist-challenged leukocytes. Fatty acid content of leukocytes and plasma was quantified in (1) samples from cows not supplemented with PUFA, (2) cows supplemented with linoleic acid (LnA), and (3) cows supplemented with α-linolenic acid (ALA). Plasma oxylipids were assessed after S. uberis or lipopolysaccharide exposure and was compared with unstimulated oxylipid profiles. Fatty acid supplementation with ALA significantly increased ALA content of blood leukocytes and plasma relative to LnA. Fatty acid supplementation affected several S. uberis-induced oxylipids, but only S. uberis-induced 15-oxoETE was greater with ALA supplementation compared with LnA. Notably, only LPS-induced 5,6 LXA4 was altered with fatty acid supplementation, but no significant effect of LnA vs. ALA treatment was identified. Future studies are needed to understand how leukocyte activation and membrane PUFA availability collectively contribute to differential oxylipid profiles.

Maternal diet of polyunsaturated fatty acid altered the cell proliferation in the dentate gyrus of hippocampus and influenced glutamatergic and serotoninergic systems of neonatal female rats.

BackgroundLong-chain polyunsaturated fatty acids (PUFAs) are major components of the phospholipids that forming the cell membrane. Insufficient availability of PUFAs during prenatal period decreases accretion of docosahexaenoic acid (DHA) in the developing brain. DHA deficiency is associated with impaired attention and cognition, and would precipitate psychiatric symptoms. However, clinical studies on the potential benefits of dietary DHA supplementation to neural development have yielded conflicting results.MethodsTo further investigate the neurochemical influence of maternal PUFAs levels, we assessed the functioning of various neurotransmitter systems including glutamatergic, dopaminergic, norepinephrinergic and serotoninergic systems in the brain of neonatal female rats by HPLC-MS/MS. Meanwhile, the cell proliferation of neonatal rats was investigated using immunefluorescence.ResultsDifferent maternal n-3 PUFAs dietary influenced the FA composition, cell proliferation in the dentate gyrus of hippocampus and the contents of γ-aminobutyric acid (GABA), glutamine (GLN), dopamine (DA) and its metabolites [3,4- dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA)], norepinephrine (NE), vanilmandelic acid (VMA) and 5-HT turnover in the brain of neonatal rats. However, the mRNA expression of key synthase of neurotransmitters remains stable.ConclusionsOur study showed that maternal deficiency of n-3 PUFAs might play an important role in central nervous system of neonatal female rats mainly through impairing the normal neurogenesis and influencing glutamatergic system and 5-HT turnover.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0236-1) contains supplementary material, which is available to authorized users.

Deficiency of Lipoprotein Lipase in Neurons Decreases AMPA Receptor Phosphorylation and Leads to Neurobehavioral Abnormalities in Mice.

Alterations in lipid metabolism have been found in several neurodegenerative disorders, including Alzheimer’s disease. Lipoprotein lipase (LPL) hydrolyzes triacylglycerides in lipoproteins and regulates lipid metabolism in multiple organs and tissues, including the central nervous system (CNS). Though many brain regions express LPL, the functions of this lipase in the CNS remain largely unknown. We developed mice with neuron-specific LPL deficiency that became obese on chow by 16 wks in homozygous mutant mice (NEXLPL-/-) and 10 mo in heterozygous mice (NEXLPL+/-). In the present study, we show that 21 mo NEXLPL+/- mice display substantial cognitive function decline including poorer learning and memory, and increased anxiety with no difference in general motor activities and exploratory behavior. These neurobehavioral abnormalities are associated with a reduction in the 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor subunit GluA1 and its phosphorylation, without any alterations in amyloid β accumulation. Importantly, a marked deficit in omega-3 and omega-6 polyunsaturated fatty acids (PUFA) in the hippocampus precedes the development of the neurobehavioral phenotype of NEXLPL+/- mice. And, a diet supplemented with n-3 PUFA can improve the learning and memory of NEXLPL+/- mice at both 10 mo and 21 mo of age. We interpret these findings to indicate that LPL regulates the availability of PUFA in the CNS and, this in turn, impacts the strength of synaptic plasticity in the brain of aging mice through the modification of AMPA receptor and its phosphorylation.