Lipid Absorption

Animals absorb and transport large quantities of lipids. A major challenge is posed by the solubility characteristics of lipids. Because they are essentially insoluble in water, they must be packaged in order to move through an aqueous environment. Since many lipids are amphipathic (have water-soluble and water insoluble moieties), they have detergent-like properties that can be harmful to membranes.

Dietary cholesterol enters the intestinal lumen and is solubilized in a bile acid micelle. Cholesterol is otherwise quite insoluble in water (solubility limit ≈ 1 µg/liter).

The transport of lipids into the intestinal epithelial cells requires their solubilization in bile acid micelles. First, the solubilization facilitates the hydrolysis of fatty acid ester bonds by the intestinal lipases. Second, the transport into the enterocytes requires the formation of a properly structured bile acid micelle.

Bile is comprised of three lipid components:
1. bile acids,
2., cholesterol, and
3. phosphatidylcholine (PC; lecithin; Fig. 1).

An excess of cholesterol relative to the two biliary amphipathic lipids (PC and bile acids) can lead to the formation of cholesterol precipitates, more commonly known as gallstones.

It is important to remember that ordinarily the major component of dietary fat is always triglyceride, not cholesterol. For example, milk and butter have very little cholesterol but are very high in triglyceride. Triglyceride (and other glycerolipids, such as phospholipids) are hydrolyzed in the intestinal lumen to yield monoglycerides and free fatty acids. These lipolysis products are then absorbed by the intestinal epithelial cells and resynthesized as

Figure 1 The major lipid components of bile. Bile acids are effective detergents and, together with phophatidylcholine and cholesterol, form micelles in the intestinal lumen. These micelles solubilize lipids and aid in their absorption by the intestinal mucosal cells.

triglycerides, phospholipids, and cholesterol esters. Thus, the intestine mediates both lipolysis (in the lumen) and re-esterification (within the epithelial cells) of dietary lipids.

The ability of the intestine to re-esterify monoglycerides and cholesterol is essential for net lipid absorption. This maintains a gradient that drives net lipid absorption from the intestinal lumen. Indeed, pharmaceutical companies have sought to develop inhibitors of cholesterol absorption that function by inhibiting the intestinal enzyme responsible for cholesterol esterification, acyl-CoA:cholesterol acyltransferase (ACAT).

Although the intestine has a large capacity for lipid absorption and esterification, it is not a lipid storage organ. It must therefore package and export absorbed lipids in order that they not accumulate. To accomplish this function, the intestine assembles the lipids into specialized particles called plasma lipoproteins.