Intestinal lipid absorption and lipoprotein formation

Abstract

Purpose of review: To summarize the evidence for the presence of two lipid absorption pathways and their regulation.

Recent findings: Lipid absorption involves hydrolysis of dietary fat in the lumen of the intestine, followed by the uptake of hydrolyzed products by enterocytes. Lipids are resynthesized in the endoplasmic reticulum and are either secreted with chylomicrons and HDLs or stored as cytoplasmic lipid droplets. Lipids in the droplets are hydrolyzed and are secreted at a later time. Secretion of lipids by the chylomicron and HDL pathways are dependent on microsomal triglyceride transfer protein (MTP) and ATP-binding cassette family A protein 1, respectively, and are regulated independently. Gene-ablation studies showed that MTP function and chylomicron assembly is essential for the absorption of triglycerides. Ablation of MTP abolishes triglyceride absorption and results in massive triglyceride accumulation in enterocytes. Although the majority of phospholipid, cholesterol, and vitamin E are absorbed through the chylomicron pathway, a significant amount of these lipids are also absorbed via the HDL pathway. Chylomicron assembly and secretion is increased by the enhanced availability of fatty acids, whereas the HDL pathway is upregulated by liver X receptor agonists.

Summary: Triglycerides are exclusively transported with chylomicrons and this process is critically dependent on MTP. In addition to chylomicrons, absorption of phospholipids, free cholesterol, retinol, and vitamin E also involves HDLs. These two pathways are complementary and are regulated independently. They may be targeted to lower lipid absorption in order to control hyperlipidemia, obesity, metabolic syndrome, steatosis, insulin resistance, atherosclerosis, and other disorders.

Figure

Intestinal lipid absorption: Dietary lipids are emulsified with bile salts and are hydrolyzed by different pancreatic lipases resulting in the generation of free fatty acids (FFA), monoacylglycerols (MAG) and free cholesterol (FC). These products are taken up by enterocytes involving various transporters and transported to the endoplasmic reticulum where they are used for the synthesis of phospholipids, triacylglycerols and cholesterol esters. These lipids are assembled into chylomicron particles using apoB48 as a scaffolding protein with the help of MTP. Alternatively, they are stored in cytosol as lipid droplets. FC can be either excreted back to the lumen via ABCAG5/ABCG8 transporters are effluxed to blood circulation by ABCA1 and apoAI.