Effects of dietary fatty acids on CVD and NASH in LDLr-knockout mice
In this project, the aim is to test whether dietary fat derived from different food sources differentially effect the development of cardiovascular disease and nonalcoholic steatohepatitis (NASH) in mice.
We hypothesize that the position of saturated fatty acid in the triacylglycerol molecule, as well as the different composition of fatty acids in the different food sources may impact degree of disease. Our main focus concentrate on food sources rich in saturated fat, such as fat from pork, cows and milk.
We will use transgenic mice in which the LDL-receptor has been deleted (Ldlr-/-.Leiden mice) as a model animal for this experiment. The LDL-receptor knockout mice will experience an accumulation of LDL and acceleration of atherosclerosis and excess deposition of fat in the liver. To achieve this, we will set up a long-term feeding trial (28 weeks) with experimental diets high in fat content, that differ only in fatty acid composition; beef tallow, pork fat, milk fat and a vegetable oil rich in unsaturated fats (omega-6). Our primary endpoint is atherosclerosis and NASH. In addition we will will investigate inflammatory markers and markers of metabolic syndrome, including insulin resistance and changes in blood cholesterol.
Number of animals applied for is 90.
These experiments can not be easily modeled or mimicked by in vitro studies. We do not expect that animals will experience pain or significant degree of discomfort. Nevertheless, animals are closely monitored on a daily basis to minimize discomfort. Number of animals in this study is calculated on the basis of power-analysis, literature searches and own experience. The animals are housed in individually ventilated cages, with controlled temperature, light regulation and humidity. Cages also contain running wheels, house and nesting material.
We hypothesize that the position of saturated fatty acid in the triacylglycerol molecule, as well as the different composition of fatty acids in the different food sources may impact degree of disease. Our main focus concentrate on food sources rich in saturated fat, such as fat from pork, cows and milk.
We will use transgenic mice in which the LDL-receptor has been deleted (Ldlr-/-.Leiden mice) as a model animal for this experiment. The LDL-receptor knockout mice will experience an accumulation of LDL and acceleration of atherosclerosis and excess deposition of fat in the liver. To achieve this, we will set up a long-term feeding trial (28 weeks) with experimental diets high in fat content, that differ only in fatty acid composition; beef tallow, pork fat, milk fat and a vegetable oil rich in unsaturated fats (omega-6). Our primary endpoint is atherosclerosis and NASH. In addition we will will investigate inflammatory markers and markers of metabolic syndrome, including insulin resistance and changes in blood cholesterol.
Number of animals applied for is 90.
These experiments can not be easily modeled or mimicked by in vitro studies. We do not expect that animals will experience pain or significant degree of discomfort. Nevertheless, animals are closely monitored on a daily basis to minimize discomfort. Number of animals in this study is calculated on the basis of power-analysis, literature searches and own experience. The animals are housed in individually ventilated cages, with controlled temperature, light regulation and humidity. Cages also contain running wheels, house and nesting material.