Introduction to Lipids and Lipoproteins

Cholesterol and triglycerides are insoluble in water and therefore these lipids must be transported in association with proteins. Lipoproteins are complex particles with a central core containing cholesterol esters and triglycerides surrounded by free cholesterol, phospholipids, and apolipoproteins, which facilitate lipoprotein formation and function. Plasma lipoproteins can be divided into seven classes based on size, lipid composition, and apolipoproteins (chylomicrons, chylomicron remnants, VLDL, IDL, LDL, HDL, and Lp (a)). Chylomicron remnants, VLDL, IDL, LDL, and Lp (a) are all pro-atherogenic while HDL is anti-atherogenic. Apolipoproteins have four major functions including 1) serving a structural role, 2) acting as ligands for lipoprotein receptors, 3) guiding the formation of lipoproteins, and 4) serving as activators or inhibitors of enzymes involved in the metabolism of lipoproteins. The exogenous lipoprotein pathway starts with the incorporation of dietary lipids into chylomicrons in the intestine. In the circulation, the triglycerides carried in chylomicrons are metabolized in muscle and adipose tissue by lipoprotein lipase releasing free fatty acids, which are subsequently metabolized by muscle and adipose tissue, and chylomicron remnants are formed. Chylomicron remnants are then taken up by the liver. The endogenous lipoprotein pathway begins in the liver with the formation of VLDL. The triglycerides carried in VLDL are metabolized in muscle and adipose tissue by lipoprotein lipase releasing free fatty acids and IDL are formed. The IDL are further metabolized to LDL, which are taken up by the LDL receptor in numerous tissues including the liver, the predominant site of uptake. Reverse cholesterol transport begins with the formation of nascent HDL by the liver and intestine. These small HDL particles can then acquire cholesterol and phospholipids that are effluxed from cells, a process mediated by ABCA1 resulting in the formation of mature HDL. Mature HDL can acquire addition cholesterol from cells via ABCG1, SR-B1, or passive diffusion. The HDL then transports the cholesterol to the liver either directly by interacting with hepatic SR-B1 or indirectly by transferring the cholesterol to VLDL or LDL, a process facilitated by CETP. Cholesterol efflux from macrophages to HDL plays an important role in protecting from the development of atherosclerosis. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG .