Fig. The production of TRLs, remnant cholesterol which induces the formation of atherosclerosis. TRLs include chylomicrons, VLDL and IDL. Their major protein component is apolipoprotein B. In the fasting state, only VLDL and IDL are present in plasma, whereas chylomicrons, VLDL and their remnants circulate under non-fasting conditions. TRLs undergoes intravascular hydrolysis by lipoprotein lipase in muscle, adipose tissue, heart and other tissues, where they provide free fatty acids for energy or storage. Upon lipolysis, chylomicrons and VLDL are depleted of TG and enriched in cholesterol, resulting in the formation of chylomicron remnants and VLDL remnants. CETP mediates major lipid transfer and exchange between HDL and TRLs. During this process, cholesteryl esters are transferred from HDL to TRLs and TG move from TRLs to HDL. In addition, the plasma HDL pool involves hydrolysis of TG in VLDL, IDL, and chylomicrons. In this process, which is catalyzed by LPL, phospholipids as well as several apolipoproteins (such as apoCI, CII, CIII) are transferred to HDL. Since most cells can degrade TG, and there are not any cells that can degrade cholesterol, the cholesterol content of TRLs is more likely to be the cause of atherosclerosis and cardiovascular disease rather than raised TG per se. Indeed, cholesterol, rather than TG accumulates in intimal foam cells and in atherosclerotic plaques, and remnant lipoproteins like LDL can enter the arterial intima. In contrast, chylomicrons are too large to enter. LPL activity at the surface of remnant particles, either at the surface of vascular endothelium or within the intima, leads to liberation of free fatty acids, monoacylglycerols, and other molecules, each of which could cause local injury and inflammation. Although other possible mechanisms have been suggested, perhaps the simplest chain of events is that high triglyceride concentrations are a marker for raised remnants rich in cholesterol, which, upon entrance into the intima, leads to low-grade inflammation, foam cell formation, atherosclerotic plaques, and ultimately cardiovascular disease and increased mortality.¹¹⁾ TRLs: triglyceride rich lipoproteins, VLDL: very large density lipoprotein, IDL: intermediate density lipoprotein, TG: triglyceride, LDL: low density lipoprotein, CETP: cholesteryl ester transfer protein, HDL: high density lipoprotein, LPL: lipoprotein lipase, CE: cholesterol ester.