<p>PUFAs serve many important biological and physiological functions within the body and are key for the structure and function of the brain. Omega-6 and omega-3 PUFAs are found in abundance in phospholipids of neuronal membranes that impart structure and function of neurons. Omega-6 PUFAs are instrumental for neurotransmission, neuronal elongation, and neuritogenesis; whereas, omega-3 PUFAs promote neuronal maturation through synaptogenesis. The types of PUFAs incorporated into neuronal membranes is especially important in determining the progression of development. The processes of neurogenesis, neuritogenesis and elongation require large amounts of PUFAs to be incorporated into the membrane phospholipids. To accommodate for the high PUFA needs, maternal dietary PUFA, especially EPA and DHA, recommendations, mobilization of fatty acids into maternal circulation increases, and the accretion rate of PUFA are increased. If maternal nutritional inadequacy of PUFAs occurs during gestation, this can result in impaired cognition, behavioral abnormalities, reduced number of neurons, decreased dendric arborization, altered myelin sheath, and a reduction in brain size. </p> <p> Even though the essentiality of PUFAs in neuronal development is widely accepted, the mechanism is not well understood. There is a lack of consensus in the current literature on the effects of individual PUFAs on each stage of neuronal development and the molecular pathways involved. Despite the inconsistent evidence, the results of numerous studies have consistently suggested that neuronal membrane PUFA composition is associated with neuronal development outcomes, such as number of neurons and neurites, neurite length, and neurotransmitter release. The varying results may be the result of methodological discrepancies with PUFA composition and concentrations, as well as the models used for neuronal development. Additionally, very few studies have taken into consideration the competitive relationship of omega-6 and omega-3 PUFAs in the body when assessing neurodevelopment. </p> <p> This thesis was focused on addressing the role of PUFAs in neuronal development and to address some of the inconsistencies in the literature. attempt to elucidate the individual roles of ALA, ARA, and EPA on neuronal membrane composition and neuronal development. The aim of the thesis research project was to assess the impact of individual PUFAs on neuronal membrane PUFA composition, the membrane n-6:n-3 ratio, and the morphology of SH-SY5Y cells during differentiation. The results of this study demonstrated that supplementation of individual PUFAs alters membrane PUFA composition and the n-6:n-3 ratio. However, there wasn’t a significant effect on neurite number with ALA, ARA, and EPA treatment. Lastly, ARA treatment decreased cell viability compared to the other treatments and the BSA control. Furthermore, additional research needs to be conducted to address other morphological measures and functional outcomes, such as neurotransmitter production and release.</p>

Yes / Abstract Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. / NIHR/EME Yorkshire Cancer Research (YCR)

A esteatose hepática não alcóolica está relacionada às causas crescentes de morbimortalidade de doenças hepáticas. Sua incidência está relacionada à obesidade e comorbidades vinculadas a esta, na qual tem despertado grande interesse na pesquisa. A modulação quantitativa da dieta pode promover ou retardar a patologia. Desta forma, terapias voltadas para retardar ou diminuir a esteatose hepática não alcóolica poderiam atenuar o dano hepático, melhorar a função hepática e reduzir sua progressão. Os objetivos do presente estudo foram: avaliar o consumo de óleos vegetais ricos em MUFAs e PUFAs usados comercialmente na prevenção ou redução da esteatose hepática analisando parâmetros do metabolismo lipídico hepático e sérico, estresse oxidativo e retardando a progressão de NAFLD. Material e Métodos: os animais foram divididos nos seguintes grupos: Controle (n=10) + HLF * (n=10); Grupo HLF * AZ (n=10); Grupo HLF* CN (n=10); Grupo HLF* S (n=10). Após 16 semanas de dieta e tratamento com os respectivos óleos, os animais foram anestesiados e o sangue retirado por punção cardíaca e os tecidos para as análises posteriores. Resultados: A oferta de uma dieta rica em gordura saturada (banha) + frutose ocasionou um aumento do peso no grupo HLF enquanto a administração dos respectivos óleos vegetais foi capaz de retardar o ganho de peso. O peso hepático e da soma dos tecidos adiposos epididimal e retroperitonial foi maior no HLF enquanto houve redução significativa no peso hepático HLF/S. O tecido retroperitonial foi menor no HLF/CN. De uma maneira geral o tratamento com os respectivos óleos vegetais diminui a esteatose em todos os grupos experimentais. A oferta de azeite extra virgem não refletiu no ganho de peso, porém o grupo teve um aumento significativo de TG e VLDL séricos, com diminuição do colesterol sérico. Avaliado histologicamente diminuiu o score de esteatose quando comparado ao HLF sendo classificado como esteatose macro e microvesicular de leve a moderada. O óleo de soja apresentou uma maior quantidade de PUFAs, sendo rico em n-6, refletiu na manutenção do peso dos animais, diminuiu a esteatose, sendo classificado como esteatatose leve, quando comparado ao HLF, porém aumentou o colesterol sérico. Apresentou um aumento de MDA e diminuição de GSH hepático. O óleo de canola devido a seu teor em ácidos graxos PUFAs (n-6 e n-3) teve maior incorporação do EPA e DHA que parecem ter evidenciado positivamente. Não apresentou alteração nos parâmetros bioquímicos e apresentou menor acúmulo de gordura hepática através da análise do percentual de gordura hepática e histopatologia, sendo caracterizado como esteatose leve. Pela peroxidação lipídica apresentou um maior acúmulo de MDA, porém um aumento de GSH. Contudo, a oferta dos respectivos óleos influenciou positivamente em diferentes mecanismos fisiológicos. / The Non-alcoholic fatty liver is related to the increasing causes of morbidity and mortality of liver diases. Its incidence is related to obesity and comorbidities linked to it, in which it has awaked great interest in the research. The disease is associated to genetic predisposition, lack of physical activity and high intake of saturated fats and fructose. Quantitative modulation of the diet may promote or retard the pathology. Thus, therapies aimed at delaying or decreasing non alcoholic hepatic steatosis could alleviate liver damage, improve liver function and reduce its progression. The objectives of the present study were: to evaluate the consumption of vegetable oils rich in commercially available MUFAs and PUFAs in the prevention or reduction of hepatic steatosis by analyzing parameters of hepatic and serum lipid metabolism, oxidative stress and delaying the progression of NAFLD. Material and Methods: animals were divided into the following groups: Control (n = 10) + HLF * (n = 10); Group HLF * AZ (n = 10); Group HLF * CN (n = 10); Group HLF * S (n = 10). After 16 weeks of diet and treatment with the respective oils, the animals were anesthetized and blood was withdrawn by cardiac puncture and tissues for further analysis. Results: The supply of a diet rich in saturated fat (lard) + fructose caused an increase in weight in the HLF group while the administration of the respective vegetable oils was able to delay the weight gain. Liver weight and sum of epididymal and retroperitoneal adipose tissues were higher in HLF while there was a significant reduction in HLF / S hepatic weight. Retroperitoneal tissue was lower in HLF / CN. In general, treatment with the respective vegetable oils decreases steatosis in all experimental groups. The supply of extra virgin olive oil did not reflect weight gain, but the group had a significant increase in serum TG and VLDL, with a decrease in serum cholesterol. Histologically it reduced the steatosis score when compared to the HLF being classified as mild to moderate macro and microvesicular steatosis. Soybean oil presented a higher amount of PUFAs, being rich in n-6, reflected in the maintenance of animal weight, decreased steatosis, being classified as mild steatosis when compared to HLF, but increased serum cholesterol. He presented an increase of MDA and decrease of hepatic GSH. Canola oil due to its content of PUFAs (n-6 and n-3) had greater incorporation of EPA and DHA than appear to have been positively evidenced. There was no alteration in the biochemical parameters and presented lower accumulation of liver fat through the analysis of the percentage of liver fat and histopathology, being characterized as mild steatosis. By the lipid peroxidation presented a greater accumulation of MDA, but an increase of GSH. However, the supply of the respective oils had a positive influence on different physiological mechanisms.

A esteatose hepática não alcóolica está relacionada às causas crescentes de morbimortalidade de doenças hepáticas. Sua incidência está relacionada à obesidade e comorbidades vinculadas a esta, na qual tem despertado grande interesse na pesquisa. A modulação quantitativa da dieta pode promover ou retardar a patologia. Desta forma, terapias voltadas para retardar ou diminuir a esteatose hepática não alcóolica poderiam atenuar o dano hepático, melhorar a função hepática e reduzir sua progressão. Os objetivos do presente estudo foram: avaliar o consumo de óleos vegetais ricos em MUFAs e PUFAs usados comercialmente na prevenção ou redução da esteatose hepática analisando parâmetros do metabolismo lipídico hepático e sérico, estresse oxidativo e retardando a progressão de NAFLD. Material e Métodos: os animais foram divididos nos seguintes grupos: Controle (n=10) + HLF * (n=10); Grupo HLF * AZ (n=10); Grupo HLF* CN (n=10); Grupo HLF* S (n=10). Após 16 semanas de dieta e tratamento com os respectivos óleos, os animais foram anestesiados e o sangue retirado por punção cardíaca e os tecidos para as análises posteriores. Resultados: A oferta de uma dieta rica em gordura saturada (banha) + frutose ocasionou um aumento do peso no grupo HLF enquanto a administração dos respectivos óleos vegetais foi capaz de retardar o ganho de peso. O peso hepático e da soma dos tecidos adiposos epididimal e retroperitonial foi maior no HLF enquanto houve redução significativa no peso hepático HLF/S. O tecido retroperitonial foi menor no HLF/CN. De uma maneira geral o tratamento com os respectivos óleos vegetais diminui a esteatose em todos os grupos experimentais. A oferta de azeite extra virgem não refletiu no ganho de peso, porém o grupo teve um aumento significativo de TG e VLDL séricos, com diminuição do colesterol sérico. Avaliado histologicamente diminuiu o score de esteatose quando comparado ao HLF sendo classificado como esteatose macro e microvesicular de leve a moderada. O óleo de soja apresentou uma maior quantidade de PUFAs, sendo rico em n-6, refletiu na manutenção do peso dos animais, diminuiu a esteatose, sendo classificado como esteatatose leve, quando comparado ao HLF, porém aumentou o colesterol sérico. Apresentou um aumento de MDA e diminuição de GSH hepático. O óleo de canola devido a seu teor em ácidos graxos PUFAs (n-6 e n-3) teve maior incorporação do EPA e DHA que parecem ter evidenciado positivamente. Não apresentou alteração nos parâmetros bioquímicos e apresentou menor acúmulo de gordura hepática através da análise do percentual de gordura hepática e histopatologia, sendo caracterizado como esteatose leve. Pela peroxidação lipídica apresentou um maior acúmulo de MDA, porém um aumento de GSH. Contudo, a oferta dos respectivos óleos influenciou positivamente em diferentes mecanismos fisiológicos. / The Non-alcoholic fatty liver is related to the increasing causes of morbidity and mortality of liver diases. Its incidence is related to obesity and comorbidities linked to it, in which it has awaked great interest in the research. The disease is associated to genetic predisposition, lack of physical activity and high intake of saturated fats and fructose. Quantitative modulation of the diet may promote or retard the pathology. Thus, therapies aimed at delaying or decreasing non alcoholic hepatic steatosis could alleviate liver damage, improve liver function and reduce its progression. The objectives of the present study were: to evaluate the consumption of vegetable oils rich in commercially available MUFAs and PUFAs in the prevention or reduction of hepatic steatosis by analyzing parameters of hepatic and serum lipid metabolism, oxidative stress and delaying the progression of NAFLD. Material and Methods: animals were divided into the following groups: Control (n = 10) + HLF * (n = 10); Group HLF * AZ (n = 10); Group HLF * CN (n = 10); Group HLF * S (n = 10). After 16 weeks of diet and treatment with the respective oils, the animals were anesthetized and blood was withdrawn by cardiac puncture and tissues for further analysis. Results: The supply of a diet rich in saturated fat (lard) + fructose caused an increase in weight in the HLF group while the administration of the respective vegetable oils was able to delay the weight gain. Liver weight and sum of epididymal and retroperitoneal adipose tissues were higher in HLF while there was a significant reduction in HLF / S hepatic weight. Retroperitoneal tissue was lower in HLF / CN. In general, treatment with the respective vegetable oils decreases steatosis in all experimental groups. The supply of extra virgin olive oil did not reflect weight gain, but the group had a significant increase in serum TG and VLDL, with a decrease in serum cholesterol. Histologically it reduced the steatosis score when compared to the HLF being classified as mild to moderate macro and microvesicular steatosis. Soybean oil presented a higher amount of PUFAs, being rich in n-6, reflected in the maintenance of animal weight, decreased steatosis, being classified as mild steatosis when compared to HLF, but increased serum cholesterol. He presented an increase of MDA and decrease of hepatic GSH. Canola oil due to its content of PUFAs (n-6 and n-3) had greater incorporation of EPA and DHA than appear to have been positively evidenced. There was no alteration in the biochemical parameters and presented lower accumulation of liver fat through the analysis of the percentage of liver fat and histopathology, being characterized as mild steatosis. By the lipid peroxidation presented a greater accumulation of MDA, but an increase of GSH. However, the supply of the respective oils had a positive influence on different physiological mechanisms.