Start Date: Jan 01, 2009
End Date: Dec 31, 2013
In the next 5 years the Lipid Metabolism Laboratory will continue to test optimal lifestyle strategies for the prevention of coronary heart disease (CHD). Human intervention studies will assess effects of supplementation with omega 3 fatty acids and plant sterols versus placebo on CHD risk factors, caloric restriction in older overweight subjects using diet either low or high in glycemic load on CHD risk factors, and an aggressive lifestyle and omega 3 fatty acid supplementation program in overweight subjects with CHD versus usual care on CHD risk factors, cognitive function, and change in coronary atheroma. Population studies will examine the interaction of diet as assessed by questionnaires, genetics as assessed by genotyping, and biochemical markers of insulin resistance, inflammation, and alterations in lipoprotein particles on CHD risk and cognitive decline in participants in the Framingham Heart Study (original cohort and offspring). Human metabolic studies will examine the effects of diets low in animal fat and cholesterol with or without fish versus average American diets on lipoprotein metabolism. We will also examine the effects of estrogens and niacin on human plasma lipoprotein metabolism. Cell studies will examine the mechanisms of action of different fatty acids on the expression of specific genes involved in reverse cholesterol transport in human liver cells and in macrophages. Our overall objectives are to develop optimal lifestyle strategies for the prevention of CHD.