The biogenesis of chylomicrons

Abstract

The absorption of dietary fat is of increasing concern given the rise of obesity not only in the United States but throughout the developed world. This review explores what happens to dietary fat within the enterocyte. Absorbed fatty acids and monoacylglycerols are required to be bound to intracellular proteins and/or to be rapidly converted to triacylglycerols to prevent cellular membrane disruption. The triacylglycerol produced at the level of the endoplasmic reticulum (ER) is either incorporated into prechylomicrons within the ER lumen or shunted to triacylglycerol storage pools. The prechylomicrons exit the ER in a specialized transport vesicle in the rate-limiting step in the intracellular transit of triacylglycerol across the enterocyte. The prechylomicrons are further processed in the Golgi and are transported to the basolateral membrane via a separate vesicular system for exocytosis into the intestinal lamina propria. Fatty acids and monoacylglycerols entering the enterocyte via the basolateral membrane are also incorporated into triacylglycerol, but the basolaterally entering lipid is much more likely to enter the triacylglycerol storage pool than the lipid entering via the apical membrane.

Figure 1

Absorption of dietary lipid and its conversion to triacylglycerol (TAG). Fatty acids (FA) and sn-2-monoacylglycerol (MAG) resulting from pancreatic TAG lipase hydrolysis of dietary TAG are absorbed by the enterocytes. The FA are then bound to either intestinal-type FA-binding protein (I-FABP) or liver-type FABP (L-FABP), and the MAG is bound to L-FABP. The FA may instead acylate CoA via the action of FA-transport protein 4 (FATP4) at the level of the endoplasmic reticulum (ER). Both FA and MAG are converted to TAG by the complex lipid–synthesizing enzymes of the ER and are incorporated into chylomicron TAG in the ER lumen. Alternatively, especially if large lipid loads are presented to the ER for TAG synthesis, the TAG formed on the cytosolic side of the ER may phase separate as TAG droplets and enter the TAG storage pool. FA entering the enterocyte via the basolateral membrane are transported to the ER, perhaps via FABPs, and are also converted to TAG. However, this TAG is more likely to enter the TAG storage pool than to be incorporated into chylomicron TAG. The FA may also be either incorporated into phospholipids (PL) or metabolized to CO₂ in the mitochondria (not shown).

Figure 2

Intracellular prechylomicron transport. The assembly of prechylomicrons occurs in the lumen of the endoplasmic reticulum (ER). After their biogenesis in the ER lumen, prechylomicrons are packaged into specialized vesicles known as prechylomicron transport vesicles (PCTVs). The average diameter of the PCTVs is ~250 nm, which is sufficient to enclose chylomicron-sized particles. PCTVs bud off the ER membrane and move to and fuse with the cis-Golgi, delivering their prechylomicron cargo to the Golgi lumen. Nascent proteins are transported from the ER to the Golgi in coat protein complex II (COPII) vesicles. Their size ranges between ~55 and 70 nm. PCTVs bud from the ER membrane in the absence of COPII proteins, whereas the protein vesicles require the COPII machinery for their budding. After processing in the Golgi, mature chylomicrons are transported to the basolateral membrane via a separate vesicular system.