Yes / Background: Oral administration of purified omega-3 (ω-3) PUFAs is associated with changes to the fecal microbiome. However, it is not known whether this effect is associated with increased PUFA concentrations in the gut. Objectives: We investigated the luminal bioavailability of oral ω-3 PUFAs (daily dose 1 g EPA and 1g DHA free fatty acid equivalents as triglycerides in soft-gel capsules, twice daily) and changes to the gut microbiome, in the ileum. Methods: Ileostomy fluid (IF) and blood were obtained at baseline, after first capsule dosing (median 2 h), and at a similar time after final dosing on day 28, in 11 individuals (median age 63 y) with a temporary ileostomy. Fatty acids were measured by LC–tandem MS. The ileal microbiome was characterized by 16S rRNA PCR and Illumina sequencing. Results: There was a mean 6.0 ± 9.8-fold and 6.6 ± 9.6-fold increase in ileal EPA and DHA concentrations (primary outcome), respectively, at 28 d, which was associated with increased RBC ω-3 PUFA content (P ≤ 0.05). The first oral dose did not increase the ileal ω-3 PUFA concentration except in 4 individuals, who displayed high luminal EPA and DHA concentrations, which reduced to concentrations similar to the overall study population at day 28, suggesting physiological adaptation. Bacteroides, Clostridium, and Streptococcus were abundant bacterial genera in the ileum. Ileal microbiome variability over time and between individuals was large, with no consistent change associated with acute ω-3 PUFA dosing. However, high concentrations of EPA and DHA in IF on day 28 were associated with higher abundance of Bacteroides (r2 > 0.86, P < 0.05) and reduced abundance of other genera, including Actinomyces (r2 > 0.94, P < 0.05). Conclusions: Oral administration of ω-3 PUFAs leads to increased luminal ω-3 PUFA concentrations and changes to the microbiome, in the ileum of individuals with a temporary ileostomy.

Les lipases sont des enzymes présentant un grand intérêt industriel. L’intérêt de ces enzymes a conduit à caractériser ces enzymes, à mieux comprendre leur mécanisme réactionnel et leur cinétique, et à établir des méthodes efficaces de production en système d’expression homologue et hétérologue. Plus récemment, l’ingénierie enzymatique permet d’améliorer les caractéristiques des enzymes. Ce thèse s’est fixé deux objectifs principaux: premièrement, la purification et la fonctionnalisation d’acides gras poly-insaturés de type Omega-3 (PUFAs), et spécialement l’acide cis-4, 7, 10, 13, 16, 19-docosahexaénoique (DHA) et deuxièmement la production de lipides structurés (SL). Un premier objectif fut de produire une molécule pharmaceutique, le nicotinyl DHA ester. Le co-substrat du DHA est le nicotinol, un alcool qui après absorption, il est rapidement converti en acide nicotinique (Vitamine B3). La trans-esterification enzymatique entre l’ester éthylique du DHA et le nicotinol a été optimisée dans le but de synthétiser un ester présentant les propriétés cumulatives des deux réactants. Après la sélection de l’enzyme optimale (lipase immobilisée de Candida antarctica; Novozyme 435) et le choix du milieu réactionnel (milieu sans solvant), le procédé a été optimisé. Une conversion supérieure à 97 % a été obtenu en 4 heures avec 45 g.L-1 d’enzyme. Dans ces conditions, une productivité de 4.2 g de produit .h-1.g d’enzyme-1 a été obtenue. Ce projet nécessite une haute pureté en DHA. Un procédé de purification enzymatique a été choisi. Les lipases sont capables de discriminer entre les acides gras en fonction de la longueur de chaine et du degré d’insaturation. Les lipases agissent par résolution cinétique, en réagissant plus efficacement avec les acides gras saturés et mono-insaturés qu’avec les PUFAs résistants. La lipase YLL2 de Yarrowia lipolytica apparait comme un bon candidat car elle est homologue à une des lipases les plus efficaces, la lipase de Thermomyces lanuginosus. YLL2 a permis d’obtenir une discrimination très efficace. Les raisons de la sélectivité de l’enzyme ont été identifiées : il s’agit du positionnement de la double liaison la plus proche de la fonction carboxylique. La concentration en DHA la plus élevée a été obtenue avec YLL2 (73%) avec un pourcentage de récupération du DHA-EE de 89%. YLL2 est par conséquent l’enzyme décrite la plus efficace pour la purification du DHA.La mutagénèse ciblée dans le site actif de YLL2 a été utilisée pour améliorer la sélectivité de cette enzyme. L’analyse de la structure 3D et les alignements avec des lipases homologues a permis de choisir les cibles de mutagénèse dirigée. Les acides aminés cibles ont été changés de manière à restreindre ou élargir le site actif. De ce premier screening de variantes deux positions ont permis d’améliorer la spécificité de l’enzyme, les positions I100 et V235. Finalement la saturation de ces 2 positions a été réalisée. Le dernier objectif de la thèse était la production de SL par acidolysis enzymatique entre l'huile d'olive vierge et les acides caprylic ou capric utilisant la lipase YLL2 immobilisé. Le SL obtenu devrait être riche en acide oléique à la position sn-2 tandis que les C8:0 et C10:0 devraient être principalement estérifiés aux positions sn-1,3. YLL2 immobilisé sur Accurel 1000 a été testé dans un système sans solvant. La réaction d’acidolysis d'huile d'olive avec C8:0 ou C10:0 a été optimisée avec la méthodologie de surface de réponse (RSM). / Lipases are enzymes with applications extended to a wide variety of industries. The variety of lipases applications led to increased research to characterize them and better understand their kinetics and reaction mechanisms and to establish methods for lipase production in homologous and heterologous expression systems. Lately enzymatic engineering allowed the improvement of lipase characteristics. This thesis project studies the use of lipases for two main objectives: lipase-catalyzed purification and functionalization of Omega-3 polyunsaturated fatty acids (PUFAs), especially cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid (DHA) and production of structured lipids (SL). DHA was used for the synthesis of a pharmaceutical molecule, the nicotinyl DHA ester. The co-substrate of the reaction was nicotinol, an alcohol from the group B pro-vitamin, which after absorption is rapidly converted into nicotinic acid (Vitamin B3). The enzymatic trans-esterification of DHA ethyl esters with nicotinol was optimised to synthesise an ester presenting the cumulative properties of the two reactants. After enzyme (immobilized lipase from Candida antarctica; Novozym 435) and reaction medium (solvent-free system) selection, the process was optimised. A conversion to nicotinyl-DHA superior to 97 % was obtained in 4 hours using 45 g.L-1 of enzyme. With a productivity of 4.2 g of product .h-1.g of enzyme-1.This project requires DHA of high purity. Enzymatic purification was chosen for the production of DHA concentrates. Lipases can discriminate between fatty acids in function of their chain length and saturation degree. Lipases react more efficiently with the bulk of saturated and mono-unsaturated fatty acids than with the PUFAs. The objective was the discovery of more specific enzymes for DHA purification. The lipase Lip2 from Yarrowia lipolytica (YLL2) appears as a good candidate since it is homologous to one of the most efficient lipase, the lipase from Thermomyces lanuginosus. YLL2 enables a high discrimination to be obtained, enzyme selectivity being principally due to the positioning of the double-bond the closest from the carboxylic group. The highest concentration of DHA was obtained with YLL2 (73%) with a recovery percentage of DHA-EE of 89%. YLL2 is the most efficient described lipase for DHA purification.Site directed mutagenesis was used to improve YLL2 from Y. lipolytica. Using its three dimensional structure and alignment with homologous lipases, targets for site directed mutagenesis were chosen. Chosen amino acids were substituted by two amino acids of different sizes. From the screening of variants two positions with promising specificities where chosen, positions I100 and V235. Finally saturation of both positions and the analysis of their performances in the selected reactions were carried out. The last objective was the production of SL by enzymatic acidolysis between virgin olive oil and caprylic or capric acids using immobilized Lip2 from Y. lipolytica. The SL obtained should be rich in oleic acid at the sn-2 position while C8:0 and C10:0 should be mainly esterified at the sn-1,3 positions. Lip2 from Y. lipolytica immobilized on Accurel MP 1000 was tested in a solvent-free system. The acidolysis reaction of olive oil with C8:0 or C10:0 was optimized by response surface methodology (RSM)

Mehrfach ungesättigte omega-3 Fettsäuren (n-3 PUFAs), wie Eicosapentaensäure (EPA) und Docosahexaensäure (DHA), schützen vor kardiovaskulären Erkrankungen, wie tödlichen Arrhythmien. In vitro Untersuchungen belegen, dass rekombinante Cytochrom P450 (CYP) Enzyme nicht nur die n-6 PUFA Arachidonsäure (AA), sondern auch die n-3 PUFAs EPA und DHA als alternative Substrate verwenden. Dabei entstehen bioaktive regio- und stereoisomere Epoxy- und Hydroxymetaboliten, CYP-Eicosanoide, die als sekundäre Botenstoffe bei der Regulation von Gefäß-, Nieren- und Herzfunktionen fungieren. Die genauen molekularen Mechanismen dieser Metabolite sind noch weitgehend unerforscht. In der vorliegenden Arbeit wurde zunächst der ernährungsbedingte Einfluss auf das endogene CYP-Eicosanoidprofil im Menschen untersucht. Die Ergebnisse der klinischen Studie zeigten, dass n-3 PUFAs auch in vivo alternative Substrate von CYP-Enzymen darstellen und wenn verfügbar sogar effektiver zu ihren Metaboliten umgesetzt wurden als AA. Als ein wichtiger Metabolit entsteht nach EPA/DHA-Supplementation 17,18-EEQ, welcher womöglich der eigentliche Vermittler der kardioprotektiven Effekte von n-3 PUFAs ist. Unter Verwendung eines etablierten Zellmodells mit spontan schlagenden neonatalen Rattenkardiomyozyten (NRKMs) wurde der anti-arrhythmische Effekte von 17,18-EEQ genauer untersucht. Der negativ chronotrope Effekt von EPA auf NRKMs wurde tatsächlich durch 17,18-EEQ vermittelt, insbesondere dem R,S-Enantiomer. Mittels Strukturfunktionsanalyse wurden synthetische Analoga mit gleicher Wirksamkeit wie dem 7,18-EEQ gefunden, wobei strikte strukturelle Merkmale für die biologische Funktion identifiziert wurden. Die Suche nach einem molekularen Ziel für CYP-Epoxyeicosanoide führte zu einem möglichen Rezeptorkandidaten, der hinsichtlich seiner Ligandenspezifität untersucht wurde. Dieser oder zukünftige andere Rezeptorkandidaten stellen ein mögliches neues zelluläres Ziel zur Behandlung kardialer Arrhythmien dar. / The n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect from cardiovascular disease, especially from fetal arrhythmia. Moreover, in vitro studies proved that recombinant cytochrome P450 (CYP) enzymes not only accept the physiologically most important n-6 PUFA arachidonic acid (AA), but also EPA and DHA as alternative substrates, thereby generating regio- and stereospecific biologically active epoxy- and hydroxymetabolites, CYP-eicosanoids. These metabolites serve as second messengers regulating vascular, renal and cardiac function. The precise underlying molecular mechanisms are only partially understood and need further investigation. The first aim of the thesis was to show that the endogenous CYP-eicosanoid profile depends on the availability of the precursor fatty acids. The results of a clinical trial with 20 volunteers, show that n-3 PUFAs serve also in vivo as alternative CYP-dependent substrates and are even preferentially metabolized compared to AA. After EPA/DHA-supplementation 17,18 EEQ was generated as a major metabolite, potentially an important mediator of cardiovascular effects originally attributed to n-3 PUFAs. To test the anti-arrhythmic effect of EPA and 17,18-EEQ, an established cell model with neonatal rat cardiomyocytes (NRKMs) was used. The negative chronotropic effect of EPA was mimicked by 17,18-EEQ, attributed only to the R,S-enantiomer. A structure activity relationship study revealed synthetic analogs, exerting the same biological effect as 17,18-EEQ. Strict structural requirements were found for agonistic function, hinting at a specific interaction with cellular targets, like GPCRs. The search of a molecular target of CYP-eicosanoids led to a putative receptor, which was tested for ligand binding specificity. If the preliminary results on the ligand binding are confirmed in future experiments this receptor might be a novel target for the treatment of cardiac arrhythmia.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

Background: Iron deficiency (ID) is the most prevalent nutritional deficiency in the world. In children, both inadequate iron and fatty acid (FA) status have been found to have an effect on cognitive and behavioural function, including physical activity behaviour and attention deficit hyperactivity disorder (ADHD)–related behaviour. Aim: To investigate the effects of supplementation with iron and omega–3 fatty acids (n–3 FAs), alone and in combination, on spontaneous motor activity and ADHD–related behaviour in iron deficient primary school children in KwaZulu–Natal. An additional aim was to evaluate the use of the Actical accelerometer as a tool to assess physical activity behaviour. Methods: The study design was a 2x2 factorial, randomized, double–blind and placebo–controlled trial. Iron deficient school children aged six to ten years with or without mild anaemia were included in the study (n = 321). Subjects were randomly assigned to receive one of the following supplement combinations: (1) 420mg docosahexaenoic acid (DHA)/80 mg eicosapentaenoic acid (EPA) + 50mg of iron as ferrous sulphate (Fe); (2) 420mg DHA/80mg EPA + placebo; (3) 50mg of Fe + placebo; (4) placebo + placebo. Supplements were provided four times a week for a duration of 8.5 months (excluding school holidays). Physical activity of a subgroup of subjects (n=98) was recorded on four random school days at baseline, midpoint and endpoint (12 days in total) during three different time periods namely class time 1 (08h00-10h30), break time (10h30–11h00) and class time 2 (11h00–12h00). Classroom behaviour of study subjects was assessed by teachers at baseline and endpoint using the Conners’ Teacher Rating Scale–Revised: Short Forms (CTRS). Iron status indicators and red blood cell (RBC) FA composition were measured at baseline and endpoint. Treatment effects were assessed for activity and CTRS scores. Furthermore, the relationship between activity, CTRS scores and iron/FA status indicators was determined using bivariate correlation and multivariate linear regression analysis. Results: Overall activity of all subjects varied over time from baseline and midpoint to endpoint. A significant cycle x age interaction (P = 0.005) as well as a significant cycle x time period x gender interaction (P = 0.036) was observed on overall activity. There were no significant interactions of cycle or time period with treatment. However, there was a significant main effect of DHA/EPA supplementation for lower class time 1 activity at endpoint (P = 0.014). Biological markers indicating better or poorer iron status were positively and negatively associated with activity at break time, respectively. Subjects in the group receiving both iron and DHA/EPA supplements showed a significant improvement from baseline to endpoint on the cognitive problems/inattention subscale (P = 0.005) of the CTRS. Hyperactivity scores increased iv significantly from baseline to endpoint in all groups (P = 0.006). DHA (r = –.203; P = 0.040) and EPA (r = –.199; P = 0.044) content of RBC were negatively associated with activity at class time 1. No significant associations were observed between activity and CTRS scores at baseline. At endpoint, class time 1 activity was positively associated with all CTRS subscale scores except for the cognitive problems subscale, which only bordered significance (correlation, P = 0.051; regression, P = 0.073). Conclusions: These findings suggest that n–3 FA supplementation may have an influence on ADHD–related behaviour during class time. During school break time when subjects were allowed to move around freely, iron status was positively associated with spontaneous motor activity. Furthermore, the accelerometer might be a useful complimentary tool for assessing both classroom and break time activity behaviour in school children. / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2012.

[Truncated abstract] The role of fish consumption and omega-3 polyunsaturated fatty acids (PUFAs) in the prevention of disease has been the subject of much investigation in recent years. A clue that these factors might be of importance was the observation that populations consuming high levels of marine omega-3 PUFAs had lower rates of morbidity and mortality from cardiovascular disease. From there, research in this area has expanded to include a range of chronic diseases and their prevention. An area of particular interest is the role of fish consumption in the prevention of various cancers. In Australia, one in three men and one in four women are expected to be diagnosed with cancer by the age of 75. Identifying preventive factors that can be translated into constructive health promotional messages is of great importance in addressing this group of diseases that has such a large impact on the health and wellbeing of the population. ... Results and conclusions Analysis of the data from the population-based case-control study suggests a protective effect of preserved fish consumption, possibly due to the high oil content of these fish. The developed questionnaire is a valid and reliable tool for measuring fish and seafood consumption as determined by regression analysis with an independent biomarker and reliability analysis using intra-class correlation. Importantly, reliability can be maintained despite asking a high level of detail from participants. For ranking according to overall fish consumption, detailed questioning is probably not necessary, however inclusion of variables representing multiple categories of fish and seafood consumption in a regression model enables us to better account for variation in blood omega-3 PUFA levels than a single variable representing overall consumption. For the purpose of questionnaire validation, plasma phospholipid and erythrocyte membrane levels of EPA and DHA are equivalent biomarkers of fish and seafood consumption. The choice between them by future investigators will be based on more practical aspects such as convenience and the fasting state of subjects. The tangible product of this thesis is additional evidence to support a protective association between fish consumption and prostate and breast cancers, and a valid and reliable questionnaire v for measuring habitual consumption of fish and seafood in a West Australian population, that could also be applied to other populations after minor adjustment for local fish and seafood consumption patterns.

Diss. (sammanfattning) Umeå : Umeå universitet, 2010.

Master of Science / Department of Animal Sciences and Industry / Joann M. Kouba / The objective of this study was to evaluate the reproductive effects of supplementing normally cycling mares with marine-derived omega-3 (n-3) fatty acids during the estrous cycle. Fifteen mares were assigned to a control diet (CONT, n=7) or a fish oil supplemented diet (FO, n=8) containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The FO mares received 18.48 g EPA/10.08 g DHA/mare/d. At the start of the trial, mares were synchronized using a progesterone and estradiol protocol. Following synchronization, mares were monitored with transrectal ultrasonography throughout the second estrous cycle. Ovarian activity, ovulation, and presence of a corpus luteum were noted. Mares were ultrasounded throughout the third estrous cycle until a 35 mm follicle was detected. Upon detection of the 35 mm follicle, hCG was administered. Within 16 hr, transvaginal ultrasound-guided follicular aspiration (TUGA) was performed on the preovulatory follicle, signifying the end of the trial. Follicular fluid was analyzed for fatty acid and hormone concentrations. Serum fatty acids were measured every 2 wk and serum hormone concentrations were analyzed during the second estrous cycle at 5 d to 1 d prior to ovulation, at ovulation, and 3 and 5 d post-ovulation. Samples were also collected prior to hCG administration and on aspiration day for hormone analysis. Serum estradiol-17β, progesterone, luteinizing hormone (LH), and insulin-like growth factor 1 (IGF-1) were measured. Fish oil supplementation increased (P < 0.01) arachidonic acid (ARA), EPA, docosapentaenoic acid (DPA), and DHA in mare serum and increased (P<0.01) EPA, DPA, and DHA in follicular fluid. No overall treatment effect was found on serum hormone concentrations during the second estrous cycle, but a decrease (P<0.05) in IGF-1 was noted in the FO group on aspiration day. Concentrations of IGF-1 were also lower (P<0.05) in follicular fluid in the FO group compared to controls. No other follicular fluid differences were observed. Supplementation resulted in a smaller diameter follicle (P<0.05, 38.0 ± 0.47 mm) on aspiration day than the CONT group (39.5 ± 0.5 mm). Dietary n-3 fatty acids modify mare serum and follicular fluid fatty acid profiles, with supplementation of EPA and DHA decreasing serum and follicular IGF-1 concentrations.

Ever since the emergence of the hypothesis that linked the aetiology of schizophrenia with abnormal membrane phospholipids composition, an increasing number of evidences have suggested reduced membrane polyunsaturated fatty acids in patients with schizophrenia. This has led to a conduct of several studies to evaluate the efficacy of omega-3 fatty acid supplement in the modification of membrane phospholipids and treatment of schizophrenia. The two main omega-3 fatty acid classes, EPA and DHA, play a vital role in membranes. This project work reviews omega-3 fatty acid studies and summarizes their outcomes. Eight original articles (nine studies) were reviewed. Six out of nine studies measured RBC membrane fatty acids levels and all six studies reported a significant increase in EPA after EPA supplement. Two studies reported increased DHA post omega-3 fatty acid and DHA supplement, respectively. One study observed a dose-dependent increment in DHA after EPA supplement. Improved symptoms were observed in seven studies, while one study found a worsening of symptoms in patients with low baseline PUFA. Moreover, out of the six studies that evaluated the correlation between symptom change and membrane fatty acids change, three studies observed a correlation between increased EPA and symptom improvement. One study reported an increased AA associated with improved symptoms, in contrast to another study, which found a correlation between increased AA and worsened symptoms. The conclusion from this project work is that EPA supplement can increase the EPA levels in membranes; however, its therapeutic effect in schizophrenia requires further investigation using larger studies. / Ända sedan tillkomsten av hypotesen som länkade etiologin av schizofreni med onormala sammansättningar av membranfosfolipider, har bevis för nedsatt membranfettsyror hos patienter med schizofreni ökat. Detta har lett till genomförandet av flera studier för att utvärdera effekten av omega-3 supplement i modifieringen av membranfosfolipider och i behandling av schizofreni. De två viktigaste omega-3 klasserna, EPA och DHA, spelar en viktig roll i membran. Detta projektarbete granskar de omega-3 studierna och sammanfattar deras resultat. Åtta originalartiklar (nio studier) granskades. Sex av nio studier mätte nivåer av RBC membranfettsyror och alla sex studierna rapporterade en signifikant ökning av EPA efter EPA behandling. Två studier rapporterade ökad DHA efter omega-3 och DHA behandling, respektive. En studie observerade en dosberoende ökning i DHA efter EPA behandling. Förbättrade symtom observerades i sju studier, medan en studie fann en försämring av symtom hos patienter med låg baseline PUFA. Av de sex studier som utvärderade sambandet mellan symtomförändring och förändring i membranfettsyror, hittade två studier samband mellan ökad EPA och symtomförbättring. En studie rapporterade en ökad AA i samband med förbättrade symtom, i motsats till en annan studie, som fann ett samband mellan ökad AA och försämrade symtom. Slutsatsen från detta projektarbete är att EPA tillägg ökar nivåer av EPA i membranfosfolipider; men dess terapeutiska effekt vid schizofreni kräver ytterligare utredning med hjälp av större studier.

Plusieurs études montrent que les acides gras (AG) oméga-3 sont bénéfiques pour la santé cardiovasculaire. Une étude antérieure dans notre laboratoire a montré que l’administration des acides gras oméga-3 réduit la taille de l'infarctus du myocarde (IM). Cependant, la question demeure de savoir si les deux principaux acides gras oméga-3 à longue chaîne, l'acide eicosapentaénoïque (EPA) et l'acide docosahexaénoïque (DHA) possèdent la même efficacité à réduire la taille de l'infarctus. Le but de ce projet sera de déterminer l’efficacité relative de chacun de ces acides gras oméga-3 à protéger le cœur dans un modèle d’ischémie/reperfusion et d’étudier certaines voies de cardioprotection. Des rats mâles adultes Sprague-Dawley ont été nourris pendant 14 jours avec une diète comprenant l'un: 1- aucun AG oméga-3; 2- 5 g d'EPA / kg de nourriture; 3- 5 g de DHA / kg de nourriture; 4- 2,5 g de chaque oméga-3 AG / kg de nourriture; 5- 5 g chaque AG oméga-3 / kg de nourriture. Par la suite, les animaux ont été soumis à une ischémie pendant 40 minutes, causée par l'occlusion de l'artère coronaire gauche descendante. Au bout de 24 heures de reperfusion, la taille de l'infarctus est déterminée. Dans un sous-groupe d'animaux, l'activité d’Akt et des caspase-3 sont mesurées dans la région ischémique après 30 minutes de reperfusion. Finalement, à 15 minutes de reperfusion, l'ouverture du pore de transition de perméabilité mitochondriale mPTP est déterminée dans un autre sous-groupe. Les résultats indiquent que les diètes EPA ou DHA réduisent de manière significative la taille de l'infarctus par rapport à la diète sans AG oméga-3, tandis que la combinaison de deux acides gras oméga-3 n'a pas montré de diminution de la taille de l'infarctus. L'activité de la caspase-3 est réduite pour le groupe DHA puis, l'activité d'Akt est augmentée avec les diètes EPA et DHA seules. Finalement, en présence d’une diète enrichie uniquement de DHA, l'ouverture des mPTP est retardée comparativement aux autres diètes. / Several studies show that fatty acids (FA) Omega-3 are beneficial for cardiovascular health. A previous study in our laboratory has shown that omega-3 intake AG reduced the size of the myocardial infarction. However the question remains whether the two main omega-3 long chain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are also effective in reducing infarct size. The purpose of this project is to determine the mechanisms by which one or other of the FA Omega-3 act to protect the myocardium. For this purpose, Sprague-Dawley adult male rats were fed for 14 days with diets comprising one of: 1- Any FA omega-3; 2- 5 mg EPA / kg diet; 3- 5 mg DHA / kg feed; 4- 2.5 mg of each omega-3 AG / kg diet; 5- 5 mg each AG omega-3 / kg of feed. Thereafter, the animals were subjected to ischemia for 40 minutes, caused by occlusion of the left coronary artery descending. At 24 hours of reperfusion, the infarct size is determined. In a subgroup of animals, the activity of caspase-3 and the activation levels of Akt are measured in the ischemic region to 30 minutes of reperfusion. And finally at 15 minutes of reperfusion, the opening of the permeability transition pore mitochondrial mPTP is determined. The results indicate that diets EPA or DHA significantly reduce the infarct size compared to the diet without FA omega-3 while the combination of two FA omega-3 did not show reduction of the infarct size. The activity of caspase-3 is reduced to the DHA group, then AKT activity is increased with EPA and DHA diets and DHA individually confers a resistance to the opening of the pore mPTP. EPA and DHA are individually effective in reducing infarct size while the combination of 2 FA is not at low concentrations.