Triacylglycerol (TG) is the most concentrated form of energy storage available to mammals. Excessive TG storage is manifested as obesity, which is a major health problem in the Western world. Obesity currently affects more than 20% of adults in North America and it is a risk factor for hypertension, diabetes and cardiovascular disease. Elevated plasma LDL cholesterol levels are directly correlated with the risk of atherosclerosis. Therefore, there is a substantial pharmacological interest in the enzymes that control TG and cholesterol metabolism in tissues. Our research is focused at elucidating the mechanism by which triacylglycerol and cholesterol are utilized by the cell. We have characterized lipases that are involved in VLDL secretion from hepatocytes and fatty acids and glycerol from adipocytes. We have now also generated genetically altered mouse models that have no expression of the lipases and are studying the consequence on lipid metabolism in vivo.