Abstract
Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting up to one-third of the adult population in western countries. NAFLD is characterised by increased lipid accumulation (especially triglycerides) in liver cells. The disease has been described by various terms including fatty liver (NAFL, steatosis) and steatohepatitis (NASH), characterised by the presence of fat in the liver and inflammation with or without fibrosis. NAFLD patients and especially those having NASH may progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Furthermore, a strong association exists between type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, arterial hypertension and NAFLD. This PhD programme of work began with the investigation of the role of glyoxalase (GLO-1) enzyme system in NAFLD (Chapter 3). The initial hypothesis was that a down-regulation of GLO 1 would occur following fatty acid treatment. Following the inability to show a significant change in GLO 1 protein expression in fatty acid-treated cells which typify NAFLD, the research study investigated the role of vitamin D as a possible nutritional factor in the progression of NAFLD (Chapter 4). Using mechanistic approaches including cell culture and enzyme- linked immunosorbent assay (ELISA), the study investigated the effects of vitamin D supplementation on the induction of cytokine secretion as markers of inflammation in NAFLD (Chapter 5). In addition, public health approaches including a systematic review and meta-analysis were utilised to explore the relationship between vitamin D and NAFLD development / progression (Chapter 6). Findings from both areas of research suggested that vitamin D may be an important marker in NAFLD patients although it may not be an actual treatment option for NAFLD: given the growing prevalence of NAFLD in different population groups, further research into the link between vitamin D and NAFLD is certainly justified