Dietary cholesterol and the mechanisms of cholesterol absorption

Cholesterol absorption occurs primarily in the duodenum and proximal jejunum at levels of efficiency that often vary greatly among individuals within any species. The absorption process is largely specific for cholesterol because plant sterols, although structurally similar to cholesterol, are absorbed either poorly or not at all. In adult humans consuming a typical Western diet, about one-third of the cholesterol that enters the small-bowel lumen daily is of dietary origin; the remainder is derived from bile and other endogenous sources. In the intraluminal phase of absorption, diet-derived lipids are hydrolyzed by pancreatic enzymes and cholesterol is incorporated into mixed micelles containing bile acid, phospholipid, fatty acid and monoacylglycerol. These micelles diffuse across the unstirred water layer, a barrier that lies between the bulk water phase and the mucosal cell. At the mucosal membrane, micellar disaggregation occurs and cholesterol crosses the membrane either passively or via a membrane protein transporter. Cholesterol then traverses the cytosol to the endoplasmic reticulum where it is esterified and incorporated into apo B-containing lipoproteins. These nascent lipoproteins are then secreted into the lymph, thus completing the absorption process. It remains to be determined which of the steps is rate limiting.