Intestinal lipid absorption

Abstract

Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as protein-independent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease.

Fig. 1.

Intestinal lipid absorption. Products of lipid hydrolysis are solubilized in micelles and presented to the apical membranes of enterocytes. This membrane harbors several transport proteins that participate in the uptake of various types of lipids. Niemann-Pick C1 like 1 (NPC1L1) is a protein involved in cholesterol uptake. CD36 and fatty acid (FA) transport protein (FATP) have been shown to participate in FA transport, whereas scavenger receptor class B type I (SR-BI) is involved in vitamin E (Vit E) uptake. In the cytosol, FA-binding protein (FABP) and cellular retinol-binding protein (CRBP) transport FAs and retinol (R), respectively. Acyl-CoA:cholesterol acyltransferase (ACAT), diacylglycerol acyltransferase (DGAT), and lecithin:retinol acyltransferase (LRAT) are found in the endoplasmic reticulum (ER) membrane, where they facilitate the esterification of cholesterol, monoacylglycerols (MAG), and retinol, respectively. These esterified products are incorporated into apolipoprotein (apo)B48-containing chylomicrons (CM) in a microsomal triglyceride (TG) transport protein (MTP)-dependent manner. The newly synthesized prechylomicrons are transported in specialized vesicles to the Golgi apparatus for further processing and for secretion. In addition, enterocytes express ATP-binding cassette (ABC) transporter A1 on the basolateral membrane to facilitate the efflux of cholesterol. C, free cholesterol; RE, retinyl ester; CE, cholesteryl ester; AIV, apolipoprotein A-IV.