Project description:The aim of this study was to assess whether chronic treatment with RPV can modulate the progression of chronic liver disease, especially of non-alcoholic fatty liver disease (NAFLD), through a nutritional model in wild-type mice Mice were daily treated with RPV (p.o.) and fed with normal or high fat diet during 3 months to induce fatty liver disease
Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
Project description:The current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated) or corn oil (polyunsaturated).