Effect of dietary fat composition on the metabolic syndrome; in vivo and in vitro studies

Background: The metabolic syndrome affects 10-35% of the European population and increases type 2 diabetes mellitus and cardiovascular disease. risk by 2.8-8 and 1.5-6 fold, respectively. Prospective evidence suggests dietary fat composition may modify components of the syndrome, including insulin resistance and endothelial dysfunction. Aim: To investigate the impact of dietary fat composition on insulin sensitivity (Si) and endothelial dysfunction. Methods: The effects of dietary fat quality and quantity were investigated.in a large (n =417), pan-European, dietary intervention trial p2 weeks), carried out in free-living participants with the metabolic syndrome. Multiple regression analysis identified key determinants of Si and endothelial dysfunction in this population and in a group of healthy, aged-matched subjects (n =239). A comparative investigation of the effects of a range of fatty acids on endothelial inflammatory gene expression was also performed using real time RT-PCR. Results: An increase in percentage energy from (%E) saturated fatty acids (SFA) decreased Si (t =0.055). Increased %E monounsaturated fatty acids (MUFA) reduced fasting insulin levels (p =0.03). The in vivo and in vitro investigations showed fat quality differentially affected endothelial function. In multiple regression analysis, key independent determinants of endothelial dysfunction and insuli~ resistance were insulin sensitivity (2.9-6.4%) and endothelial function (1.9-5.3%), respectively. Waist, gender, triacylglycerol and non-esterified fatty acid levels were also important determinants of Si. Results showed gender specific effects on the responsiveness of some metabolic factors to dietary intervention and also suggested disease state may be important. Conclusion: Substitution of SFA for MUFA may represent a strategy to improve insulin sensitivity in those with the metabo'lic syndrome. However, the practical attainment of an adequate level of substitution may be a limiting factor. Further work is required to elucidate the role of insulin action in the effects of fatty acids on endothelial function.EThOS - Electronic Theses Online ServiceGBUnited Kingdo