Osmotrophic glucose and leucine assimilation and its impact on EPA and DHA content in algae.
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ABSTRACT:
SUBMITTER: Peltomaa ET
PROVIDER: S-EPMC6944096 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite numerous studies investigating n-3 long chain polyunsaturated fatty acid (LCPUFA) supplementation and inflammatory bowel diseases (IBD), the extent to which dietary n-3 LCPUFAs incorporate in gastrointestinal (GI) tissues and correlate with red blood cell (RBC) n-3 LCPUFA content is unknown. In this study, mice were fed three diets with increasing percent of energy (%en) derived from eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA). Dietary levels reflected recommended intakes of fish/fish oil by the American Heart Association. We analyzed the FA composition of phospholipids extracted from RBCs, plasma, and GI tissues. We observed that the 0.1%en EPA+DHA diet was sufficient to significantly increase the omega-3 index (RBC EPA+DHA) after 5 week feeding. The baseline EPA levels were 0.2-0.6% across all tissues increasing to 1.6-4.3% in the highest EPA+DHA diet; these changes resulted in absolute increases of 1.4-3.9% EPA across tissues. The baseline DHA levels were 2.2-5.9% across all tissues increasing to 5.8-10.5% in the highest EPA+DHA diet; these changes resulted in absolute increases of 3.2-5.7% DHA across tissues. These increases in EPA and DHA across all tissues resulted in strong (r>0.91) and significant (P<0.001) linear correlations between the omega-3 index and plasma/GI tissue EPA+DHA content, suggesting that the omega-3 index reflects the relative amounts of EPA+DHA in GI tissues. These data demonstrate that the GI tissues are highly responsive to dietary LCPUFA supplementation and that the omega-3 index can serve as a valid biomarker for assessing dietary EPA+DHA incorporation into GI tissues.
| S-EPMC4127132 | biostudies-literature
Project description:At a population level, cardioprotective and cognitive actions of the fish oil (FO) derived long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been extensively demonstrated. In addition to dietary intake, which is limited for many individuals, EPA and DHA status is dependent on the efficiency of their biosynthesis from ?-linolenic acid. Gender and common gene variants have been identified as influencing the rate-limiting desaturase and elongase enzymes. Response to a particular intake or status is also highly heterogeneous and likely influenced by genetic variants which impact on EPA and DHA metabolism and tissue partitioning, transcription factor activity, or physiological end-point regulation. Here, available literature relating genotype to tissue LC n-3 PUFA status and response to FO intervention is considered. It is concluded that the available evidence is relatively limited, with much of the variability unexplained, though APOE and FADS genotypes are emerging as being important. Although genotype × LC n-3 PUFA interactions have been described for a number of phenotypes, few have been confirmed in independent studies. A more comprehensive understanding of the genetic, physiological and behavioural modulators of EPA and DHA status and response to intervention is needed to allow refinement of current dietary LC n-3 PUFA recommendations and stratification of advice to "vulnerable" and responsive subgroups.
| S-EPMC4808853 | biostudies-literature
Project description:Previous research showed that increasing the proportion of docosahexaenoic acid (DHA) in marine lipid supplements significantly reduces associated health benefits compared with balanced eicosapentaenoic acid (EPA):DHA supplementation Dasilva et al., 2015 [1]. It was therefore hypothesized that the EPA and DHA molecules might have differential resistance to oxidation during gastric digestion and that the oxidation level achieved could be inversely correlated with intestinal absorption and, hence, with the resultant health benefits. Accordingly, we tested this proposed mechanism of action by investigating the degree of oxidation in the stomach, and the levels of bioaccessible lipids, of varying molar proportions of DHA and EPA (2:1, 1:1 and 1:2) using the dynamic gastrointestinal tract model TIM-1. In addition, small intestine enterocyte absorption and metabolism were simulated by Caco-2 cell monolayers that were incubated with these same varying proportions of DHA and EPA, and comparing oxidized and nonoxidized polyunsaturated fatty acids (PUFAs). The results show an inverse correlation between lipid oxidation products in the stomach and the levels of bioaccessible lipids. The balanced 1:1 EPA:DHA diet resulted in lower oxidation of PUFAs during stomach digestion relative to the other ratios tested. Finally, cell-based studies showed significantly lower assimilation of oxidized EPA and DHA substrates compared to nonoxidized PUFAs, as well as significant differences between the net uptake of EPA and DHA. Overall, the present work suggests that the correct design of diets and/or supplements containing marine lipids can strongly influence the stability and bioaccessibility of PUFAs during gastrointestinal digestion and subsequent absorption. This could modulate their health benefits related with inflammation, oxidative stress and metabolic disorders.
| S-EPMC6364551 | biostudies-literature
Project description:The aim of this study was to explore how individual differences in content of the omega-3 fatty acids EPA and DHA in skeletal muscle of slaughter-sized Atlantic salmon, are associated with expression of genes involved in key metabolic processes. All experimental fish were fed the same diet throughout life and fasted for 14 days prior to slaughter. Still, there were relatively large individual variations in EPA and DHA content of skeletal muscle. Higher DHA content was concurrent with increased expression of genes of the glycolytic pathway and the production of pyruvate and lactate, whereas EPA was associated with increased expression of pentose phosphate pathway and glycogen breakdown genes. Furthermore, EPA, but not DHA, was associated with expression of genes involved in insulin signaling. Expression of genes specific for skeletal muscle function were positively associated with both EPA and DHA. EPA and DHA were also associated with expression of genes related to eicosanoid and resolvin production. EPA was negatively associated with expression of genes involved in lipid catabolism. Thus, a possible reason why some individuals have a higher level of EPA in the skeletal muscle is that they deposit - rather than oxidize - EPA for energy.
| S-EPMC6405848 | biostudies-other
Project description:Microalgae have the ability to synthetize many compounds, some of which have been recognized as a source of functional ingredients for nutraceuticals with positive health effects. One well-known example is the long-chain polyunsaturated fatty acids (PUFAs), which are essential for human nutrition. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the two most important long-chain omega-3 (ω-3) PUFAs involved in human physiology, and both industries are almost exclusively based on microalgae. In addition, algae produce phytosterols that reduce serum cholesterol. Here we determined the growth rates, biomass yields, PUFA and sterol content, and daily gain of eight strains of marine cryptophytes. The maximal growth rates of the cryptophytes varied between 0.34-0.70 divisions day-1, which is relatively good in relation to previously screened algal taxa. The studied cryptophytes were extremely rich in ω-3 PUFAs, especially in EPA and DHA (range 5.8-12.5 and 0.8-6.1 µg mg dry weight-1, respectively), but their sterol concentrations were low. Among the studied strains, Storeatula major was superior in PUFA production, and it also produces all PUFAs, i.e., α-linolenic acid (ALA), stearidonic acid (SDA), EPA, and DHA, which is rare in phytoplankton in general. We conclude that marine cryptophytes are a good alternative for the ecologically sustainable and profitable production of health-promoting lipids.
| S-EPMC5793051 | biostudies-literature
Project description:EPA and DHA protect against multiple metabolic and neurologic disorders. Although DHA appears more effective for neuroinflammatory conditions, EPA is more beneficial for depression. However, the brain contains negligible amounts of EPA, and dietary supplements fail to increase it appreciably. We tested the hypothesis that this failure is due to absorption of EPA as triacylglycerol, whereas the transporter at the blood-brain barrier requires EPA as lysophosphatidylcholine (LPC). We compared tissue uptake in normal mice gavaged with equal amounts (3.3 μmol/day) of either LPC-EPA or free EPA (surrogate for current supplements) for 15 days and also measured target gene expression. Compared with the no-EPA control, LPC-EPA increased brain EPA >100-fold (from 0.03 to 4 μmol/g); free EPA had little effect. Furthermore, LPC-EPA, but not free EPA, increased brain DHA 2-fold. Free EPA increased EPA in adipose tissue, and both supplements increased EPA and DHA in the liver and heart. Only LPC-EPA increased EPA and DHA in the retina, and expression of brain-derived neurotrophic factor, cyclic AMP response element binding protein, and 5-hydroxy tryptamine (serotonin) receptor 1A in the brain. These novel results show that brain EPA can be increased through diet. Because LPC-EPA increased both EPA and DHA in the brain, it may help in the treatment of depression as well as neuroinflammatory diseases, such as Alzheimer's disease.
| S-EPMC6399499 | biostudies-literature
Project description:Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury "from within" and chronic changes that may prove both morbid and fatal. The resolution phase of inflammation, once thought to be a passive event, is now known to be a highly regulated, active, and complex program that terminates the inflammatory response once the threat has been contained. Specialized pro-resolving mediators (SPMs) are biosynthesized from omega-3 essential fatty acids to resolvins, protectins, and maresins and from omega-6 fatty acids to lipoxins. Through cell-specific actions mediated through select receptors, these SPMs are potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages, promoting a return to tissue homeostasis. This process appears to be defective in several common human lung diseases, such as asthma and COPD, which are characterized by chronic unrestrained inflammation and significant associated morbidity. Here, we highlight translational research in animal models of disease and with human subjects that sheds light on this rapidly evolving area of science and review the molecular and cellular components of the resolution of lung inflammation.
| S-EPMC4854800 | biostudies-other
Project description:The importance of n-3 long chain polyunsaturated fatty acids (LC-PUFAs) for human health has received more focus the last decades, and the global consumption of n-3 LC-PUFA has increased. Seafood, the natural n-3 LC-PUFA source, is harvested beyond a sustainable capacity, and it is therefore imperative to develop alternative n-3 LC-PUFA sources for both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Genera of algae such as Nannochloropsis, Schizochytrium, Isochrysis and Phaedactylum within the kingdom Chromista have received attention due to their ability to produce n-3 LC-PUFAs. Knowledge of LC-PUFA synthesis and its regulation in algae at the molecular level is fragmentary and represents a bottleneck for attempts to enhance the n-3 LC-PUFA levels for industrial production. In the present review, Phaeodactylum tricornutum has been used to exemplify the synthesis and compartmentalization of n-3 LC-PUFAs. Based on recent transcriptome data a co-expression network of 106 genes involved in lipid metabolism has been created. Together with recent molecular biological and metabolic studies, a model pathway for n-3 LC-PUFA synthesis in P. tricornutum has been proposed, and is compared to industrialized species of Chromista. Limitations of the n-3 LC-PUFA synthesis by enzymes such as thioesterases, elongases, acyl-CoA synthetases and acyltransferases are discussed and metabolic bottlenecks are hypothesized such as the supply of the acetyl-CoA and NADPH. A future industrialization will depend on optimization of chemical compositions and increased biomass production, which can be achieved by exploitation of the physiological potential, by selective breeding and by genetic engineering.
| S-EPMC3853752 | biostudies-literature
Project description:Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction. We hypothesized that differences in clinical efficacy of various omega-3 FA preparations could result from differential effects on membrane structure. To test this, we used small-angle X-ray diffraction to compare 1-palmitoyl-2-eicosapentaenoyl-sn-glycero-3-phosphocholine (PL-EPA), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PL-DHA), and 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PL-AA) in membranes with and without 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol. Electron density profiles (electrons/Å3 vs. Å) were used to determine membrane structure, including membrane width (d-space). PL-EPA and PL-DHA had similar membrane structures without POPC and/or cholesterol but had contrasting effects in the presence of POPC and cholesterol. PL-EPA increased membrane hydrocarbon core electron density over an area of ±0-10 Å from the center, indicating an extended orientation. PL-DHA increased electron density in the phospholipid head group region, concomitant with disordering in the hydrocarbon core and a similar d-space (58 Å). Adding equimolar amounts of PL-EPA and PL-DHA produced changes that were attenuated compared with their separate effects. PL-AA increased electron density centered ±12 Å from the membrane center. The contrasting effects of PL-EPA, PL-DHA, and PL-AA on membrane structure may contribute to differences observed in the biological activities and clinical actions of various omega-3 FAs.
| S-EPMC8430377 | biostudies-literature
Project description:Maternal dietary supplementation of n-3 polyunsaturated fatty acids (n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is considered to play positive roles in fetal neuro system development. However, maternal n-3 PUFAs may induce molecular reprogramming of uncommitted fetal myoblasts into adipocyte phenotype, in turn affecting lipid metabolism and energy expenditure of the offspring. The objective of this in vitro study was to investigate the combined effects of EPA and DHA on C2C12 cells undergoing brown adipogenic differentiation. C2C12 myoblasts were cultured to confluency and then treated with brown adipogenic differentiation medium with and without 50 μM EPA and 50 μM DHA. After differentiation, mRNA and protein samples were collected. Gene expression and protein levels were analyzed by real-time PCR and western blot. General Proteomics analysis was conducted using mass spectrometric evaluation. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XFP Analyzer. Cells treated with n-3 PUFAs had significantly less (P < 0.05) expression of the brown adipocyte marker genes PGC1α, DIO2, and UCP3. Expression of mitochondrial biogenesis-related genes TFAM, PGC1α, and PGC1β were significantly downregulated (P < 0.05) by n-3 PUFAs treatment. Expression of mitochondrial electron transportation chain (ETC)-regulated genes were significantly inhibited (P < 0.05) by n-3 PUFAs, including ATP5J2, COX7a1, and COX8b. Mass spectrometric and western blot evaluation showed protein levels of enzymes which regulate the ETC and Krebs cycle, including ATP synthase α and β (F1F0 complex), citrate synthase, succinate CO-A ligase, succinate dehydrogenase (complex II), ubiquinol-cytochrome c reductase complex subunits (complex III), aconitate hydratase, cytochrome c, and pyruvate carboxylase were all decreased in the n-3 PUFAs group (P < 0.05). Genomic and proteomic changes were accompanied by mitochondrial dysfunction, represented by significantly reduced oxygen consumption rate, ATP production, and proton leak (P < 0.05). This study suggested that EPA and DHA may alter the BAT fate of myoblasts by inhibiting mitochondrial biogenesis and activity and induce white-like adipogenesis, shifting the metabolism from lipid oxidation to synthesis.
| S-EPMC7303889 | biostudies-literature