Chylomicron Metabolism

Since the intestine is primarily an absorptive organ, it must have the means of exporting newly absorbed lipids. The enterocyte re-esterifies fatty acids and monoglycerides to form triglycerides and phospholipids. Absorbed cholesterol is esterified to form cholesterol esters. Under ordinary circumstances, the vast majority of the core lipids in the chylomicron are triglycerides; however, after a cholesterol-rich meal, the intestine manufactures cholesterol ester-rich chylomicron particles. Triglycerides and cholesterol esters are then packaged into the core of chylomicrons, which are secreted into the lymphatics. By secreting chylomicrons into the lymphatics, they gain entrance into the general circulation via the thoracic duct. This guarantees that extrahepatic tissues, principally adipose tissue and muscle, are the first to be exposed to the newly secreted chylomicrons—if chylomicrons were secreted directly into the bloodstream, they would first be delivered to the liver via the portal vein.

TABLE I Buoyant Density and Size of Plasma Lipoproteins

Class	Density (g/ml)	Diameter (nm)
Chylomicrons	0.93	75–1200
VLDL	0.93–1.006	30–80
IDL	1.006–1.019	25–35
LDL	1.019–1.063	18–25
HDL2	1.063–1.125	9–12
HDL3	1.125–1.210	5–9

Chylomicrons are very large (up to 1 μm in diameter). Thus a plasma sample containing chylomicrons is milky in appearance. A sample of fasting plasma is typically clear in appearance, even if there is an elevation in LDL particles—LDL particles are not large enough to scatter light.

In terms of net transport, the bulk of lipid flux is triglyceride → adipose tissue and muscle. How is the triglyceride transferred from the chylomicron particle to these tissues? As was the case with the transfer of lipids from the intestinal lumen to the intestinal epithelial cells, this transfer begins with a lipolytic reaction to convert an oily lipid, triglyceride, into an amphipathic lipid, free fatty acid. In this case, the reaction is catalyzed by lipoprotein lipase, an enzyme that resides at the luminal surface of the capillary endothelium in adipose tissue and muscle.

Class	Chol	PL	Protein	TG	CE
Chylomicrons	2	7	2	86	3
VLDL	7	18	8	55	12
IDL	9	9	19	23	29
LDL	8	22	22	6	42
HDL2	5	33	40	5	17
HDL3	4	35	55	3	13
a Values represent percent of dry mass. Chol, cholesterol; PL, phospholipids; TG, triglycerides; CE, cholesterol esters.

Main Features of Chylomicron Metabolism

• Chylomicrons are exclusively synthesized in the intestine.
• They are the package of dietary fat. Thus, few chylomicrons are made in fasted people.
• They are usually >80% triglyceride.
• They are secreted into the lymphatics, rather than the bloodstream.
• They are acted upon by lipoprotein lipase on the surface of adipose and muscle capillaries.
• After depletion of their triglyceride via the lipoprotein lipase reaction, the resulting remnants are cleared from the circulation.
• Chylomicrons are not converted into LDL.

Lipoprotein lipase catalyzes the complete hydrolysis of triglycerides to free fatty acid and glycerol. This reaction occurs in the bloodstream, while the chylomicron particle is in proximity to the endothelial surface of the capillary wall. Cholesterol ester is not a substrate for lipoprotein lipase. Therefore, with the selective loss of triglycerides, the particle becomes more enriched in cholesterol ester. The free fatty acids are then taken up and oxidized in muscle or re-esterified and stored as triglyceride droplets in adipose tissue. The abundance of the adipose form of lipoprotein lipase is increased by insulin, thus promoting uptake of free fatty acids and storage as cytoplasmic triglyceride droplets (see Fig. 4).

Figure 4 Chylomicron pathway. The intestine secretes chylomicron particles into the lymphatics. They gain entrance into the general circulation through the thoracic duct. Lipoprotein lipase, on the luminal surface of adipose and muscle capillary endothelial cells, hydrolyzes the triglyceride core to free fatty acids and glycerol. The free fatty acids are re-esterified and stored as triglycerides in adipose tissue or undergo β-oxidation in muscle. The lipid-depleted chylomicrons, chylomicron remnants, are cleared by the liver through a pathway that depends on apolipoprotein-E as a ligand for cellular receptors.

A chylomicron that has been depleted of its triglyceride core is termed a chylomicron remnant. Chylomicron remnants are cleared from the circulation, primarily by the liver.