La mucoviscidose est une maladie génétique présentant des altérations ioniques causées par une protéine membranaire défectueuse ou inexistante la CFTR entraînant des perturbations métaboliques. Nous sommes intéressés à l’altération du métabolisme des acides gras polyinsaturés (AGPI) n-3 et n-6, caractérisé par une déficience en acides linoléique (LA) et docosahexaénoïque (DHA) et une élévation de l’acide arachidonique (AA). Ce déséquilibre peut être préjudiciable à l’état des patients du fait du rôle clé de certains AGPI à différents niveaux de la vie. Nos travaux ont portés sur la recherche des bénéfices d’un vecteur riche en un AGPI n-3 d’intérêt, le DHA, dans le contexte de la mucoviscidose à travers deux approches : une approche par supplémentation réalisée chez un modèle murin présentant la mutation la plus répandue chez les patients, et une approche sur un modèle d’entérocyte humain afin d’étudier de façon plus approfondie l’intérêt du supplément sur la fonctionnalité cellulaire (absorption des nutriments lipidiques). Nos résultats nous ont conduits à différentes conclusions : les souris delF508 nourries avec du Peptamen Junior présentent une perturbation du métabolisme des n-6 (LA, AA) dès l’âge de 3 mois ; cette altération apparaît mais plus tard sous régime standard. Par contre, quelque soit le régime alimentaire notre modèle ne développe pas de déficience en DHA jusqu’à l’âge d’1 an. L’évolution du statut en AGPI n-6 est donc dépendante du régime et de l’âge. L’apport de glycérophospholipides enrichis en DHA administré à faible dose permet de corriger les perturbations en AGPI n-6 et d’augmenter le rapport en DHA/AA dans la plupart des organes. Ce vecteur s’avère potentiellement intéressant en nutrithérapie chez le patient. Un enrichissement physiologique en DHA de l’entérocyte ne modifie pas ses capacités absorptives qui sont plutôt régulées par le type de particules véhiculant les produits de lipolyses, micelles de sels biliaires versus liposomes. / Cystic fibrosis is a genetic disease showing ionic alterations, caused by an absent or defective membrane protein CFTR leading to metabolic disturbances. We are interested in n-6 and n-3 polyunsaturated fatty acid (PUFA) metabolism alteration characterized by a linoleic (LA) and docosahexaenoic (DHA) acids deficiency and high level of arachidonic acid (AA). This imbalance can affect patient health due to the key role of some PUFAs in different levels of life. Our studies focused on finding the benefits of a vector enriched in one interesting n-3 PUFA, DHA, in context of cystic fibrosis, through two approaches: a nutritional supplementation conducted in a mouse model with the most common mutation of cystic fibrosis patients, and an approach on a model of human enterocyte to investigate more thoroughly the effect of the vector on cell functionality (absorption of lipid nutrients). Our results led us to different conclusions: del F508 mice fed with Peptamen Junior have a metabolic disorder of the n-6 PUFA (LA, AA) at the age of 3 months, but this alteration appears later under standard regime . But, whatever the diet, our model does not develop a DHA deficiency to the age of 1 year. The changing status of n-6 is dependent on diet and age. Glycerophospholipids enriched in DHA given at low doses can correct disturbances in PUFA n-6 and increase the DHA/AA ratio in most organs. This vector is potentially interesting for a patient nutritherapy. A physiological DHA enrichment of enterocyte does not alter its absorption capacity, which is rather regulated by the type of particles carrying the lipolysis products, bile salt micelles versus liposomes.

Dentro da perspectiva da utilização de compostos fenólicos como antioxidantes naturais para minimizar os efeitos in vitro e in vivo do processo oxidativo dos lípides insaturados, foi realizada a monitoração dietética de duas dietas ricas em lípides das séries ω3 e ω6 e a suplementação de um chá de uma mistura de especiarias, em ratos Wistar, com o objetivo de verificar a influência dos compostos fenólicos, presentes nas especiarias, sobre o metabolismo de ácidos graxos das séries ω3 e ω6. Extratos e frações das especiarias mostarda, canela e erva doce foram obtidos e tiveram suas atividades antioxidantes testadas em sistemas aquoso (cooxidação de substratos com o uso de ácido linoléico/β-caroteno) e lipídico (RANCIMAT) e o perfil de compostos fenólicos identificados e quantificados por CGMS. A partir de uma mistura de especiarias, foi elaborado um chá que foi fornecido aos animais de cada grupo dietético (ω3 e ω6). Após 45 dias de tratamento, os animais foram sacrificados e tiveram seus tecidos coletados para análise de TBARs e do perfil lipídico por CGMS. Todos os extratos das especiarias apresentaram atividade antioxidante equivalente ou superior ao BHT. Foram identificados por CGMS os ácidos fenólicos: catecol, salicílico e caféico. Foi obtido nos tecidos dos animais que o somatório do perfil de ácidos graxos saturados e dos insaturados apresentaram diferença entre os grupos testes e controles. Logo, no tecido cerebral, o EPA foi incorporado apenas no grupo ω3 que recebeu o extrato das especiarias. Já para o DHA, do mesmo grupo dietético, os tecidos hepático e renal também apresentaram incorporação aumentada em relação ao controle. No grupo dietético ω6, destaca-se um aumento no percentual de incorporação do ácido linoléico nos tecidos cardíaco e renal no grupo experimental. Enquanto, para o ácido araquidônico, houve diferença em todos os tecidos. Já, para os resultados da lipoperoxidação, observou-se que todos os tecidos dos animais que receberam o extrato das especiarias apresentaram baixos valores em comparação aos seus respectivos controles. Este estudo também avaliou a ação de compostos fenólicos do chá da mistura das especiarias mostarda, canela e erva doce sobre as enzimas lipoxigenase e cicloxigenase. O extrato da mistura das especiarias a 100 e 200 ppm foi adicionado no meio de reação contendo o substrato e a enzima lipoxigenase 1B da Sigma com 112.000 und/mg. A cicloxigenase foi obtida de vesículas seminais de carneiro e seguiu-se o mesmo protocolo de atividade para a lipoxigenase. Indometacina foi o inibidor utilizado como controle positivo da reação. Observou-se que a 200 ppm, como na concentração do chá (0,02%), a lipoxigenase foi inibida em aproximadamente em 90%. Já para a cicloxigenase, o extrato a 200 ppm resultou numa média de 75% de inibição da atividade da enzima, enquanto que a indomentacina apresentou uma média de 77% de inibição. A absorção aparente do chá das especiarias indicou que os fenólicos presentes na mistura foram absorvidos em média de 75%. O estudo histopatológico dos intestinos delgados dos animais não apresentou nenhuma diferença na área de absorção entre o grupo experimental e o controle. Estes dados sugerem, portanto, um efeito antioxidante das substâncias fenólicas identificadas nas especiarias sobre os ácidos graxos das séries ω3 e ω6, podendo agir diretamente: (1) no alimento (óleo), (2) com modificação do perfil lipídico, (3) proteção quanto à oxidação de tecidos e (4) inibição das enzimas da biossíntese dos eicosanóides. / Considering the perspective for the use of phenolic compounds as natural antioxidants to minimize in vitro and in vivo effects of oxidative processes on unsaturated lipids, this work monitored Wistar rats fed with two diets rich in ω3 and ω6 polyunsaturated lipids, supplemented with tea made from a blend of spices. The objective of the work was to study the influence of phenolic compounds present in spices on the metabolism of ω3 and ω6 fatty acids. Extracts and fractions of mustard, cinnamon and anise were obtained and had their antioxidant activity tested in aqueous (co-oxidation of substrates using linoleic acid/β-carotene) and lipidic systems (RANCIMAT). Their phenolic compounds profile was determined and quantified using CGMS. The rats of each diet group (ω3 and ω6) were given tea made from a blend of spices and sacrificed after 45 days. Their tissues were then collected and analyses of TBARS and lipid profile were performed using CGMS. Ali the extracts of spices showed equal or higher antioxidant activity than BHT. The following phenolic acids were identified using CGMS: cathecol, salicilic and cafeic. It was observed that the total amount of the profile of saturated and unsaturated fatty acids in the rat tissues were different in the test group and the control group. In brain tissue, EPA was found only in the ω3 diet group which was given the tea. Concerning DHA, liver and kidney tissues of the same diet group showed higher concentrations than the control group. In the ω6 diet group, an outstanding increase of linoleic acid in cardiac and kidney tissues was found. Concerning the arachidonic acid, a difference in concentration was observed in ali tissues. Ali the tissues from rats given the tea presented a lower level of lipid peroxidation than their respective control groups. The present research also evaluated the action of phenolic compounds found in the tea made from the blend of mustard, cinnamon and anise on the enzymes lipoxygenase and cycloxygenase. The extract of the blend of spices, in the concentrations of 100 and 200 ppm, was added to the substrate and Sigma lipoxygenase 112.000 units/mg. Cycloxygenase was obtained from sheep seminal bladders and underwent the same protocol as lipoxygenase. Indomethacin was the inhibitor used as the positive control of the reaction. It was observed that in the concentration of 200 ppm (that is 0.02%, the same concentration as in the tea), lipoxygenase presented an average 90% inhibition. The extract of cycloxygenase 200 ppm presented 75% inhibition of the enzyme activity, while indomethacin presented an average 77% inhibition. It was found that around 75% of the phenolic compounds present in the tea made from the blend of spices were absorbed, thus leading to the conclusion that apparent absorption of the tea took place. Histopathologic examinations on the small intestines of the rats did not reveal any difference in the absorption area between the experimental and the control groups. Such results suggest therefore an antioxidant effect of the phenolic substances identified in the spices on the ω3 and ω6 fatty acids, this effect being possible directly (1) on the food (oil) , (2) modification of the profile fatty acids, (3) oxidation protection tissues and, (4) inhibition of enzymes of eicosanoids biosinthesys.

[pt] A teoria moderna de carteiras estabelece que a alocação ótima de ativos é uma função da média-variância da distribuição dos retornos. Na prática, estes retornos são modelados por distribuições Gaussianas e seus parâmetros são estimados a partir dos dados históricos do mercado, utilizando técnicas descritivas da estatística Frequentista. A dinâmica atual dos mercados globalizados gera períodos aleatórios de alta e baixa volatilidade e/ou saltos nos retornos dos ativos, provocando mudanças de regime ou quebras estruturais na série temporal dos retornos, tornando-os não Gaussianos. Consequentemente, a teoria moderna de carteiras precisa ser adaptada para atender a estas novas condições do mercado. Para contornar o problema das mudanças de regime, propõe-se a substituição do mecanismo de otimização baseada no índice de Sharpe pela otimização baseada na medida Ômega. Isto porque a medida Ômega tem a vantagem de quantificar o risco-retorno de qualquer distribuição de probabilidade e não somente distribuições Gaussianas como acontece com o índice de Sharpe, ou seja, as distribuições de retornos não Gaussianos provocadas pelas mudanças de regime são tratadas naturalmente pela medida Ômega. Para contornar o problema das quebras estruturais, propõe-se a substituição do procedimento de estimação dos parâmetros da distribuição dos retornos, baseada em técnicas da estatística Frequentista por técnicas da estatística Bayesiana. Isto porque a estatística Bayesiana, tem a vantagem de combinar as informações públicas do mercado (dados históricos dos retornos) com informações privadas do investidor (visões prospectivas do mercado) permitindo corrigir a quebra estrutural e, na sequência, tratar o retorno não Gaussiano, utilizando o mecanismo de otimização baseada na medida Ômega. / [en] Modern portfolio theory states that the optimal asset allocation is a function of the mean-variance of the distribution of returns. In practice, these returns are modeled by Gaussian distributions and their parameters are estimated from historical market data, using descriptive techniques of Frequentist statistics. The current dynamics of globalized markets generate random periods of high and low volatility and/or jumps in asset returns, causing regime shifts or structural breaks in the time series of returns, making them non Gaussian. Consequently, modern portfolio theory needs to be adapted to meet these new market conditions. To circumvent the problem of regime shifts, it is proposed to replace the optimization mechanism based on the Sharpe index by the optimization based on the Omega measure. This is because the Omega measure has the advantage of quantifying the risk-return of any probability distribution and not only Gaussian distributions as with the Sharpe index, that is, non Gaussian returns distributions caused by regime shifts are treated naturally by the Omega measure. To circumvent the problem of structural breaks, it is proposed to replace the estimation procedure for the parameters of the distribution of returns, based on Frequentist statistics techniques, by Bayesian statistical techniques. This is because the Bayesian statistic has the advantage of combining public market information (historical return data) with private investor information (prospective market views) allowing to correct the structural break, and subsequently, treating the non Gaussian return using the optimization based on the Omega measure.

The 2007–2009 financial crisis led to a decrease in consumer and investor confidence worldwide (SARB, 2008:2). Along with the weakened business sentiment and consumer demand, tightened funding conditions in financial markets, increased inflationary pressures, and declining global manufacturing activities, the world economic recession that followed the collapse of the world financial sector led to an estimated wealth destruction of approximately US$50 trillion (SARB, 2008:2; Aisen & Franken, 2010:3; Karunanayake et al., 2010). Apart from this estimate, the International Monetary Fund (IMF) also projected that the global bank balance sheets in advanced countries suffered losses of approximately US$4 trillion during the period 2009–2010 (Aisen & Franken, 2010:3). As a result, investors have become more risk-adverse (Guiso et al., 2013:1), and the consequences of the financial crisis, made insurable profitable investment decisions extremely difficult as market volatility tends to increase during crises periods (Karunanayake et al., 2010; Schwert, 1989:83). With the financial environment in distress, some fund managers consider equities as the preferred asset class to protect the purchasing power of their clients (Ivan, 2013). However, the studies of Ennis and Sebastian (2003) and Nicholas (2004) found evidence that hedge funds will outperform equity markets during a downswing in financial markets. In addition, hedge funds are considered market-neutral due to these investment funds’ unrestricted investment flexibility and more efficient market timing abilities (Ennis & Sebastian, 2003). Hedge funds are also considered to be more unconventional assets for improving portfolio diversification (Lamm, 1999:87), where the variation of investment strategies available in a hedge fund has the ability to satisfy investors with several different risk preferences (Shin, 2012). Still, a number of previous studies have debated conflicting evidence regarding the performance of hedge funds and the persistence in outperforming other markets. This led to the objective of this study; to evaluate the risk-adjusted performance of US and EU hedge funds compared to the associated world equity markets over the 2007–2009 financial crisis. The evidence from this study confirmed the dominance of hedge funds over the CAC 40, DAX, S&P 500 and Dow Jones, from 2004 to 2011, emphasising that the performance of the US and EU hedge funds would overshadow a normal buy-and-hold strategy on the world equity markets under investigation. Overall, the Sharpe-, Sortino-, Jensen’s alpha-, Treynor- and Calmar ratios illustrated that US hedge funds outperformed both EU hedge funds and the associated equity markets over this period. The presence of non-normality among the return distributions led to the use of the Omega ratio as the proper benchmark, which also confirmed the outperformance of US hedge funds over EU hedge funds and associated world equity markets. / MCom (Risk Management), North-West University, Vaal Triangle Campus, 2014

Performance measurement is an integral part of investment analysis and risk management. Investment performance comprises two primary elements, namely; risk and return. The measurement of return is more straightforward compared with the measurement of risk: the latter is stochastic and thus requires more complex computation. Risk and return should, however, not be considered in isolation by investors as these elements are interlinked according to modern portfolio theory (MPT). The assembly of risk and return into a risk-adjusted number is an essential responsibility of performance measurement as it is meaningless to compare funds with dissimilar expected returns and risks by focusing solely on total return values. Since the advent of MPT performance evaluation has been conducted within the risk-return or mean-variance framework. Traditional, liner performance measures, such as the Sharpe ratio, do, however, have their drawbacks despite their widespread use and copious interpretations. The first problem explores the characterisation of hedge fund returns which lead to standard methods of assessing the risks and rewards of these funds being misleading and inappropriate. Volatility measures such as the Sharpe ratio, which are based on mean-variance theory, are generally unsuitable for dealing with asymmetric return distributions. The distribution of hedge fund returns deviates significantly from normality consequentially rendering volatility measures ill-suited for hedge fund returns due to not incorporating higher order moments of the returns distribution. Investors, nevertheless, rely on traditional performance measures to evaluate the risk-adjusted performance of (these) investments. Also, these traditional risk-adjusted performance measures were developed specifically for traditional investments (i.e. non-dynamic and or linear investments). Hedge funds also embrace a variety of strategies, styles and securities, all of which emphasises the necessity for risk management measures and techniques designed specifically for these dynamic funds. The second problem recognises that traditional risk-adjusted performance measures are not complete as they do not implicitly include or measure all components of risk. These traditional performance measures can therefore be considered one dimensional as each measure includes only a particular component or type of risk and leaves other risk components or dimensions untouched. Dynamic, sophisticated investments – such as those pursued by hedge funds – are often characterised by multi-risk dimensionality. The different risk types to which hedge funds are exposed substantiates the fact that volatility does not capture all inherent hedge fund risk factors. Also, no single existing measure captures the entire spectrum of risks. Therefore, traditional risk measurement methods must be modified, or performance measures that consider the components (factors) of risk left untouched (unconsidered) by the traditional performance measures should be considered alongside traditional performance appraisal measures. Moreover, the 2007-9 global financial crisis also set off an essential debate of whether risks are being measured appropriately and, in-turn, the re-evaluation of risk analysis methods and techniques. The need to continuously augment existing and devise new techniques to measure financial risk are paramount given the continuous development and ever-increasing sophistication of financial markets and the hedge fund industry. This thesis explores the named problems facing modern financial risk management in a hedge fund portfolio context through three objectives. The aim of this thesis is to critically evaluate whether the novel performance measures included provide investors with additional information, to traditional performance measures, when making hedge fund investment decisions. The Sharpe ratio is taken as the primary representative of traditional performance measures given its widespread use and also for being the hedge fund industry’s performance metric of choice. The objectives have been accomplished through the modification, altered use or alternative application of existing risk assessment techniques and through the development of new techniques, when traditional or older techniques proved to be inadequate. / PhD (Risk Management), North-West University, Potchefstroom Campus, 2014

Performance measurement is an integral part of investment analysis and risk management. Investment performance comprises two primary elements, namely; risk and return. The measurement of return is more straightforward compared with the measurement of risk: the latter is stochastic and thus requires more complex computation. Risk and return should, however, not be considered in isolation by investors as these elements are interlinked according to modern portfolio theory (MPT). The assembly of risk and return into a risk-adjusted number is an essential responsibility of performance measurement as it is meaningless to compare funds with dissimilar expected returns and risks by focusing solely on total return values. Since the advent of MPT performance evaluation has been conducted within the risk-return or mean-variance framework. Traditional, liner performance measures, such as the Sharpe ratio, do, however, have their drawbacks despite their widespread use and copious interpretations. The first problem explores the characterisation of hedge fund returns which lead to standard methods of assessing the risks and rewards of these funds being misleading and inappropriate. Volatility measures such as the Sharpe ratio, which are based on mean-variance theory, are generally unsuitable for dealing with asymmetric return distributions. The distribution of hedge fund returns deviates significantly from normality consequentially rendering volatility measures ill-suited for hedge fund returns due to not incorporating higher order moments of the returns distribution. Investors, nevertheless, rely on traditional performance measures to evaluate the risk-adjusted performance of (these) investments. Also, these traditional risk-adjusted performance measures were developed specifically for traditional investments (i.e. non-dynamic and or linear investments). Hedge funds also embrace a variety of strategies, styles and securities, all of which emphasises the necessity for risk management measures and techniques designed specifically for these dynamic funds. The second problem recognises that traditional risk-adjusted performance measures are not complete as they do not implicitly include or measure all components of risk. These traditional performance measures can therefore be considered one dimensional as each measure includes only a particular component or type of risk and leaves other risk components or dimensions untouched. Dynamic, sophisticated investments – such as those pursued by hedge funds – are often characterised by multi-risk dimensionality. The different risk types to which hedge funds are exposed substantiates the fact that volatility does not capture all inherent hedge fund risk factors. Also, no single existing measure captures the entire spectrum of risks. Therefore, traditional risk measurement methods must be modified, or performance measures that consider the components (factors) of risk left untouched (unconsidered) by the traditional performance measures should be considered alongside traditional performance appraisal measures. Moreover, the 2007-9 global financial crisis also set off an essential debate of whether risks are being measured appropriately and, in-turn, the re-evaluation of risk analysis methods and techniques. The need to continuously augment existing and devise new techniques to measure financial risk are paramount given the continuous development and ever-increasing sophistication of financial markets and the hedge fund industry. This thesis explores the named problems facing modern financial risk management in a hedge fund portfolio context through three objectives. The aim of this thesis is to critically evaluate whether the novel performance measures included provide investors with additional information, to traditional performance measures, when making hedge fund investment decisions. The Sharpe ratio is taken as the primary representative of traditional performance measures given its widespread use and also for being the hedge fund industry’s performance metric of choice. The objectives have been accomplished through the modification, altered use or alternative application of existing risk assessment techniques and through the development of new techniques, when traditional or older techniques proved to be inadequate. / PhD (Risk Management), North-West University, Potchefstroom Campus, 2014

The 2007–2009 financial crisis led to a decrease in consumer and investor confidence worldwide (SARB, 2008:2). Along with the weakened business sentiment and consumer demand, tightened funding conditions in financial markets, increased inflationary pressures, and declining global manufacturing activities, the world economic recession that followed the collapse of the world financial sector led to an estimated wealth destruction of approximately US$50 trillion (SARB, 2008:2; Aisen & Franken, 2010:3; Karunanayake et al., 2010). Apart from this estimate, the International Monetary Fund (IMF) also projected that the global bank balance sheets in advanced countries suffered losses of approximately US$4 trillion during the period 2009–2010 (Aisen & Franken, 2010:3). As a result, investors have become more risk-adverse (Guiso et al., 2013:1), and the consequences of the financial crisis, made insurable profitable investment decisions extremely difficult as market volatility tends to increase during crises periods (Karunanayake et al., 2010; Schwert, 1989:83). With the financial environment in distress, some fund managers consider equities as the preferred asset class to protect the purchasing power of their clients (Ivan, 2013). However, the studies of Ennis and Sebastian (2003) and Nicholas (2004) found evidence that hedge funds will outperform equity markets during a downswing in financial markets. In addition, hedge funds are considered market-neutral due to these investment funds’ unrestricted investment flexibility and more efficient market timing abilities (Ennis & Sebastian, 2003). Hedge funds are also considered to be more unconventional assets for improving portfolio diversification (Lamm, 1999:87), where the variation of investment strategies available in a hedge fund has the ability to satisfy investors with several different risk preferences (Shin, 2012). Still, a number of previous studies have debated conflicting evidence regarding the performance of hedge funds and the persistence in outperforming other markets. This led to the objective of this study; to evaluate the risk-adjusted performance of US and EU hedge funds compared to the associated world equity markets over the 2007–2009 financial crisis. The evidence from this study confirmed the dominance of hedge funds over the CAC 40, DAX, S&P 500 and Dow Jones, from 2004 to 2011, emphasising that the performance of the US and EU hedge funds would overshadow a normal buy-and-hold strategy on the world equity markets under investigation. Overall, the Sharpe-, Sortino-, Jensen’s alpha-, Treynor- and Calmar ratios illustrated that US hedge funds outperformed both EU hedge funds and the associated equity markets over this period. The presence of non-normality among the return distributions led to the use of the Omega ratio as the proper benchmark, which also confirmed the outperformance of US hedge funds over EU hedge funds and associated world equity markets. / MCom (Risk Management), North-West University, Vaal Triangle Campus, 2014

Master of Science / Department of Animal Sciences and Industry / J. Ernest Minton / It has been well documented that omega-3 PUFA (n-3 PUFA) can confer a wide variety of health benefits to humans and animals. The current study was designed to evaluate the ability of n-3 PUFA to modulate the innate immune response in two diverse breeds of horses. Ten Quarter Horse and 10 American Miniature Horse mares were assigned to either an n-3 PUFA supplemented or control diet (5 full-sized and 5 miniature mares/treatment) for 56 d. The treatment diet was designed to deliver 64.4 mg/kg BW combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) daily. Whole blood (20 mL) was collected via jugular veinipuncture into heparinized tubes on 0 d, 28 d, and 56 d. Serum PUFA analysis was conducted by gas chromatography. Peripheral blood mononuclear cell (PBMC) production of tumor necrosis factor-alpha (TNFalpha) in response to toll-like receptor (TLR) ligands lipopolysaccharide (LPS), flagellin, and lipoteichoic acid (LTA) was estimated using an equine-specific ELISA. Peripheral blood samples from d 56 were also analyzed for total and differential leukocyte counts and subjected to flow cytometric analysis. Body type did not affect basal or TLR stimulated TNFα production. Serum PUFA analysis revealed a decrease in linoleic acid (LA) and substantial increases in arachidonic acid (ARA), EPA, DHA, and docosapentaenoic acid (DPA) at both d 28 and 56 in horses fed n-3 PUFA (P less than 0.0001 for all). Dietary n-3 PUFA supplementation reduced (P less than 0.05) un-stimulated basal, but not TLR stimulated TNFalpha production by PBMC’s. Supplementation with n-3 PUFA did not affect total or differential leukocyte counts, nor selected cell surface markers. These results suggest that n-3 PUFA supplementation in the horse can modify circulating PUFA and alter the inflammatory response by reducing basal TNFalpha production. Furthermore, under conditions of the current study and considering the endpoints evaluated, the American Miniature Horse could potentially be used as a model for full-sized horse breeds.

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.

Eggs enriched with omega-3 polyunsaturated fatty acids (PUFA), particularly the longer chain PUFA (LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) can boost human consumption of these fatty acids implicated in human health. Alpha-linolenic acid (ALA) from plant seeds/oils, primarily serve as the source of omega-3 PUFA for hens, however, the scarcity of ALA-rich plants and the limited conversion of ALA to LCPUFA are challenges for egg enrichment. Two major experiments were conducted to determine potential factors regulating egg enrichment of omega-3 LCPUFA based on detailed assessment of PUFA profiles in different lipid pools of hen tissues. In experiment 1, supplementation of graded levels of hempseed products, provided ~ 0.1 to 1.3% of ALA in the diets. Experiment 2, investigated dietary supplementation of flaxseed oil (ALA-rich) and algal DHA (preformed LCPUFA), each providing similar graded levels of total omega-3 PUFA. Both ALA-containing models demonstrated a plateau in DHA enrichment of eggs at higher ALA intakes. ALA-containing diets led to high concentrations of ALA in the triacylglycerol (TAG) fraction of eggs and plasma, and the adipose tissue of flaxseed oil-fed hens. In total phospholipid (PL), particularly the phosphatidylethanolamine (PE), the levels of EPA and ALA in the yolk were linearly associated with those in the liver. In all tissues, DHA dominated the PE pool, exhibiting a plateau with a strong inverse correlation to the ratio of ALA to EPA in the liver, suggesting limited ALA availability for egg DHA enrichment. The use of algal DHA should therefore permit further accumulation of DHA in the total PL and TAG fractions of yolk. However, enrichment via preformed DHA (at 3.36% algal product) was also limited by hepatic PL resulting in more DHA and EPA being shunted to the adipose TAG, concurrent with elevated hepatic acyl-CoA synthetase (ACSL1) expression. As a function of total omega-3 PUFA intakes (regardless of source), similar levels of stearidonic acid (SDA) and particularly EPA accumulated in liver PE. Therefore, hepatic PL regulation, possibly aimed at maintaining EPA level, may potentially be limiting the amount of ALA accumulation in the same pool, hence limiting the endogenous synthesis of DHA and subsequent enrichment in eggs. / February 2017