Non-alcoholic fatty liver disease

Obesity is a problem of positive energy balance, favouring an increase in energy storage over energy utilization. Parallel with increase in obesity, there is an increase in obesity-associated diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). NAFLD has become the most common cause of liver disease worldwide. The early stage of NAFLD starts with lipid accumulation in the liver which is also known as hepatic steatosis. This benign state of NAFLD may, however, evolve into non-alcoholic steatohepatitis (NASH), a condition of inflamed liver, which can further progress to liver fibrosis, cirrhosis and ultimately hepatocellular carcinoma (HCC).

The pathogenesis of NAFLD and the mechanisms responsible for disease progression are not fully understood. The research described in this thesis was performed to gain more insights into the etiology, progression and effect of risk factors in the development of NAFLD. We focus on the relationship between old age and inflammation, both of which are risk factors for the development of NAFLD and highlight the role of target gene ablations such as macroH2A1 and the fatty acid transporter CD36 in the development of NAFLD. Using animal models and a diet intervention strategy, we show the influence of parameters such as chronic obesity, ageing, CD36, and macroH2A1 in the development of NAFLD. Our data clearly suggest that a broad spectrum of genetically and environmentally originated factors are involved in the development of NAFLD. These factors, however, require more research and understanding to pave a path to treatment for NAFLD.

http://irs.ub.rug.nl/ppn/386087628

Dissertation: http://irs.ub.rug.nl/ppn/386087628