Triglycerides (TG) enter the blood from exogenous (food) and endogenous (liver) sources. Food provides neutral fat, which is primarily triglyceride and which is hydrolyzed by pancreatic lipase into free fatty acids (FFA) and monoglycerides. These enter small intestine mucosal cells. The lipid fractions are recombined into TG within the mucosal cells and are incorporated into chylomicrons. Chylomicrons have a thin outer shell of phospholipid and unesterified cholesterol with protein that is mostly in the form of apoproteins B-48, C-II, and E (the outer shell components collectively are known as “polar lipids”). There is a central core of TG plus some cholesterol esters (“non-polar lipids”). Chylomicrons give postprandial plasma its characteristic milky appearance.

Chylomicrons enter the capillaries of adipose tissue, heart muscle, and skeletal muscle where an enzyme called lipoprotein lipase that is activated by apo C-II splits off much of the TG and hydrolyzes it to FFA and glycerol. FFA are used for energy in heart and skeletal muscle. Some is transported to the liver bound to albumin and some is converted back to TG by reesterification with glycerol in fat cells and stored there for future use. The remainder of the chylomicrons (now called “chylomicron remnants,” composed mostly of apo B, apo E, and cholesterol) is taken to the liver and metabolized there.

The liver synthesizes triglyceride from FFA and glycerol derived partly from chylomicron origin and partially from hepatic synthesis by the glucose metabolism pathway. The liver also synthesizes cholesterol, cholesterol esters, apo B-100 and C-II and combines these with TG to form very low-density lipoprotein (VLDL), which is structurally rather similar to chylomicrons. In body tissues, lipoprotein lipase (activated by apo C-II) hydrolyzes TG to release FFA, leaving a “VLDL remnant.” This is taken to the liver, where about half is converted to low density lipoprotein (LDL) by addition of cholesterol esters derived from action on free cholesterol by an enzyme called lecithin-cholesterol acyltransferase (LCAT). LCAT is partially located in the liver and partially in high density lipoprotein (HDL).

Body cholesterol is derived from exogenous dietary sources and from endogenous synthesis by the liver from acetate. The majority is produced by the liver. The liver excretes some cholesterol as a component of bile.

LDL differs from VLDL in that LDL has lower triglyceride content, higher cholesterol content, and no C or E apoproteins. LDL molecules are taken into tissue cells from specific receptor sites in the cell membrane. Inside the cell, the LDL molecules are metabolized into their component parts. Some of the cholesterol is used by the cell, and some can leave the cell under proper conditions. Thus, LDLs are thought to have a major role in providing body cells with cholesterol and thereby are an important part of the atherogenic process.

HDLs have two contrasting roles in lipid metabolism. On one hand, they help create LDL from VLDL and thus enhance the possibility of atherogenesis. On the other hand, they are thought to help transport cholesterol out of peripheral tissues to the liver (although the mechanism for this is still not completely understood) and thus help “protect” against atherosclerosis.