| Summary: | The first chapter (Introduction) of the thesis summarises the pathogenesis of NAFLD and its associated risk factors such as type 2 diabetes and cardiovascular disease. Moreover, it describes: a) the potential beneficial effects of long chain omega-3 fatty acid treatment [docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA)] in NAFLD; b) the effect of genotypes patatin-like phospholipase domain-containing protein-3 (PNPLA3 I148M) and the transmembrane 6 superfamily member 2 protein (TM6SF2 E167K), on the level of DHA and EPA enrichment and end of study liver fat percentage after DHA+EPA treatment; and c) the effect of fatty acid desaturase (FADS) and Elongase (ELOVL) polymorphisms influencing omega-3 fatty acid metabolism. The second chapter describes the overall aim of this thesis. The aim of my research was to investigate in patients with NAFLD: a) the effect of long-chain omega-3 fatty acid treatment on liver fat percentage and liver fibrosis biomarkers; b) the effect of genotypes influencing NAFLD severity on treatment with DHA+EPA; and c) the effect of genotypes influencing omega-3 fatty acid metabolism in NAFLD. The third chapter describes in details the design and methods used in my research. Chapter four highlights my novel results from the WELCOME study. This chapter describes the baseline and end of study characteristics of the WELCOME study participants and shows the results of the DHA+EPA treatment on liver fat percentage and liver fibrosis biomarkers. This chapter also describes the association between DHA erythrocyte enrichment and decrease in liver fat percentage after DHA+EPA treatment. Chapter five illustrates the association between PNPLA3 I148M and DHA erythrocyte enrichment percentage and end of study liver fat percentage after DHA+EPA treatment. The chapter shows that PNPLA3 I148M was associated with higher end of study liver fat percentage and lower DHA tissue enrichment. Chapter six shows the negative association between FADS polymorphisms and omega-3 fatty acid metabolism in NAFLD. The chapter also shows that there was a gene-DHA+EPA interaction between the minor allele of the FADS1 rs174556 and Δ-5 desaturase activity after treatment with DHA+EPA. Finally, chapter seven, summarises my results in the context of current evidence and knowledge about the subject matter.
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