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Effects of fish oil and its combination with grape seed polyphenols or buckwheat d-fagomine on cardiometabolic risk factors and oxidative stress in rats

  • Autores: Bernat Miralles Pérez
  • Directores de la Tesis: Marta Romeu Ferran (dir. tes.)
  • Lectura: En la Universitat Rovira i Virgili ( España ) en 2021
  • Idioma: español
  • Tribunal Calificador de la Tesis: Josep Lluís Torres Simón (presid.), Maria Rosa Nogués i Llort (secret.), Eunice María Molinar Toribio (voc.)
  • Programa de doctorado: Programa de Doctorado en Biomedicina por la Universidad Rovira i Virgili
  • Materias:
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    • Tesis en acceso abierto en: TDX
  • Resumen
    • The past few decades have seen an alarming increase in the worldwide prevalence of obesity, atherogenic dyslipidemia, and metabolic syndrome. The increase in the prevalence of these conditions is highly related to unhealthy dietary habits and sedentary lifestyles. Overload of dietary fat promotes disturbances in several cardiometabolic processes, among which we find the onset and progression of insulin resistance. The pathogenesis of insulin resistance is clearly related to oxidative stress, inflammation as well as accumulation of bioactive lipids such as diacylglycerols and ceramides.

      The replacement of saturated fatty acids to unsaturated fatty acids exerts beneficial influence on cardiometabolic health in healthy individuals and in individuals at high risk of disease. Concretely, ω-3 polyunsaturated fatty acids (ω-3 PUFA) from fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with lower risk for developing cardiometabolic disorders. There is accumulating evidence that, when provided individually, DHA may exert more potent effects than EPA. Despite that, DHA is especially susceptible to peroxidation. Then, when provided in excess, DHA may lead to deleterious effects on health. Antioxidant compounds such as polyphenols from grape seeds can prevent oxidation of PUFA during digestion as well as in cell membranes, suggesting that the combination of ω-3 PUFA and polyphenols could exert great benefits on cardiometabolic health. On the other hand, buckwheat D-fagomine, which is an iminocyclitol capable of acting on gut microbiota, can reduce post-prandial glucose and can prevent the activation of pro-inflammatory pathways induced by lipopolysaccharides. Thus, the combination of D-fagomine and ω-3 PUFA could also potentially enhance cardiometabolic health through early acting on gut microbiota.

      The aim of the present thesis is to explore the influence of fish oil and its combination with grape seed polyphenols or buckwheat D-fagomine on cardiometabolic risk factors and oxidative stress in healthy rats and in rats fed a high fat diet.

      The first part of this thesis evaluates the effects of a fish oil rich in DHA on cardiometabolic risk factors and oxidative stress in healthy rats compared to fish oil containing EPA/DHA in a balanced 1:1 ratio, soybean oil, and coconut oil. Fish oil rich in DHA provides greater benefits on plasma lipid profile and fat accumulation in muscle than the obtained with fish oil containing EPA/DHA 1:1, but markedly promotes oxidative damage to lipids and proteins, with a concomitant increase in antioxidant response.

      The second part of this thesis evaluates the effects of fish oil containing EPA/DHA 1:1 and its combination with grape seed polyphenols on oxidative stress and bioactive lipid accumulation in the liver of rats fed a high-fat high-sucrose diet. The supplementation with fish oil containing EPA/DHA 1:1 clearly increases abundances of PUFA-containing diacylglycerols, whereas individual supplementation with grape seed polyphenols markedly decreases abundances of hepatic lipids, and potentiates the endogenous antioxidant response. Unlike individual supplementations, the combination of fish oil containing EPA/DHA 1:1 and polyphenols induces similar accumulation of monounsaturated fatty acid-containing diacylglycerols and ceramides in the liver than that induced by the high-fat diet without supplementation. Nevertheless, individual supplementations are not as effective as combined supplementation to prevent the onset of insulin resistance under fat overload conditions, suggesting that the combined supplementation promotes accumulation of fat in lipid droplets.

      The final part of this thesis evaluates the effects of fish oil containing EPA/DHA 1:1 and its combination with buckwheat D-fagomine on oxidative stress and related cardiometabolic risk factor in rats fed a high-fat diet. The supplementation with fish oil containing EPA/DHA 1:1 is the main responsible for the beneficial effects on oxidative stress observed under fat overload conditions. Nevertheless, individual supplementations are not as effective as combined supplementation to prevent the onset of insulin resistance. The combination of fish oil containing EPA/DHA 1:1 and its combination with buckwheat D-fagomine also enhances glutathione status and decreases antioxidant enzyme activities, suggesting lower oxidative stress.

      The increase in dietary intake of ω-3 PUFA from fish oil supplements containing EPA/DHA 1:1, alone or combined with polyphenols or D-fagomine, may be a useful nutritional strategy to protect against the mechanism underlying the onset of cardiometabolic disorders in healthy individuals and in individuals at high risk of disease.


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