| dc.description.abstract | Introduction: In Norway, 58 % of men and 47 % of women are classified as overweight or obese, which is a large increase since the mid-1980s. An often occurring consequence of obesity is accumulation of lipids in liver, which is often categorized as non-alcoholic fatty liver disease (NAFLD). NAFLD can further develop into NASH and cirrhosis, which is a leading cause for liver transplantations. The only current treatment against NAFLD is lifestyle change and a healthier diet. Investigating how different diets affect bodyweight and liver health is therefore important for public health. Materials and methods: Liver tissue was sampled from a total of 89 female wild-type C57BL/6N mice from five independent diet-intervention studies, in which mice were either fasted, or fed a high fat-cholesterol-sucrose (HFS) diet, a high fat diet (HF), a high fat ketogenic diet (HFK) or a methionine and choline deficient diet (MCD). We measured bodyweight, fat mass, liver mass, liver TAG, and hepatic gene and protein expression. Expression of selected genes was measured with RT-qPCR, while expression of the lipid droplet binding proteins Plin2 and Plin3 was measured with western blotting. Results: 24 hours of fasting led to reduced bodyweight and fat mass, and increased accumulation of fatty acids incorporated into triacylglycerol in liver. This was accompanied by increased expression of genes related to lipid droplet binding and lipid oxidation, and a decreased expression of genes related to lipogenesis. When comparing the diets with a high fat content, the HFS diet was the only diet that increased bodyweight and resulted in accumulation of liver fat. Furthermore, all high fat diets increased expression of genes related to lipid droplet binding and fatty acid oxidation. The HFK and HF diets with a low content of carbohydrates reduced the expression of the fatty acid synthesis genes Acc and Fasn, while this was not the case for the carbohydrate-rich HFS diet. The MCD diet, which is a model of NASH, induced a substantial loss of fat mass and increased hepatic fat accumulation, as well as increased inflammatory gene expression. Lastly, all diets increased the abundance of the Plin2 protein in liver, which indicate increased levels of lipid droplets. Conclusion: A diet rich in fat, cholesterol and sucrose led to increased adiposity and more severe steatosis compared to high fat or ketogenic diets. Such a diet, often termed “Western diet”, also induced the expression of genes related to lipogenesis, which may indicate that high sucrose feeding favours active lipogenesis in liver regardless of the level of lipid intake. Only the MCD diet resulted in significant inflammation in parallel with accumulation of liver fat, indicative of NASH. In future studies, serum cholesterol, insulin resistance and liver histology should be measured to get a broader understanding of the metabolic effects these various diets have on the overall liver health. | eng |