Chylomicrons are microscopic packages designed to transport dietary fats throughout the body after digestion. These particles move large, water-insoluble lipid molecules through the water-based environment of the bloodstream. They are the largest of the lipoprotein particles and play a primary role in the initial processing of dietary fat and fat-soluble vitamins. Their creation, delivery, and removal are highly regulated processes that ensure tissues receive necessary energy and building blocks from food.
Structure and Composition
Chylomicrons are complex particles classified as lipoproteins because they consist of a lipid core surrounded by a stabilizing shell of protein and other molecules. The center, or core, of the chylomicron is composed primarily of non-polar lipids, mainly triglycerides (83–92%) and cholesterol esters, which are highly water-insoluble. This arrangement allows the particle to efficiently carry a large amount of fat through the aqueous environment of the body.
The outer layer is a single membrane composed of more water-friendly molecules, including phospholipids, free cholesterol, and apolipoproteins. These proteins serve both structural and functional purposes, helping to emulsify the fat core and acting as signals for enzyme and receptor interaction. The main structural protein, unique to chylomicrons, is apolipoprotein B-48 (ApoB-48), a truncated version of the ApoB-100 found in other lipoproteins.
The Assembly Line: Formation and Release
The creation of chylomicrons begins inside the enterocytes, which are the specialized cells lining the small intestine. After a meal, dietary triglycerides and cholesterol are broken down in the intestinal lumen and then absorbed into these cells. Inside the enterocytes, the fatty acids and monoglycerides are re-esterified to form new triglycerides and cholesterol esters.
These newly synthesized lipids are combined with the structural protein ApoB-48 and phospholipids in a two-step process involving the endoplasmic reticulum. The package then moves through the Golgi apparatus before being secreted out of the enterocyte. These large particles are too big to enter the capillaries directly, so they are released into the lymphatic system through specialized vessels called lacteals.
The chylomicrons travel through the lymphatic vessels to the thoracic duct, which eventually drains into the bloodstream near the heart. Upon entering the circulation, these particles are considered “nascent” and acquire additional apolipoproteins, such as ApoC-II and ApoE, from high-density lipoprotein (HDL) particles. ApoC-II is a necessary cofactor for the next stage of fat delivery.
The Delivery Route: Function in the Body
The function of the chylomicron is to deliver the vast majority of its core triglycerides to peripheral tissues, such as muscle and adipose (fat) tissue. This delivery process occurs as the chylomicron travels through the capillaries lining these tissues. The acquired apolipoprotein ApoC-II activates an enzyme called lipoprotein lipase (LPL), which is anchored to the inner lining of the blood vessel walls.
LPL acts on the chylomicron by hydrolyzing, or breaking down, the triglycerides within the core into free fatty acids and glycerol. These free fatty acids are then immediately absorbed by the adjacent muscle cells for energy or by fat cells for storage. As LPL continues to remove triglycerides, the chylomicron shrinks significantly in size, losing much of its lipid cargo.
This intense lipolysis causes the particle to shed some of its surface components, including ApoC-II, which returns to the HDL pool. The transfer of ApoC-II off the chylomicron effectively deactivates LPL, stopping the breakdown of the remaining lipids. The entire process ensures that dietary fat is rapidly distributed to tissues that need it for immediate fuel or for long-term energy reserves.
Clearing the Traffic: Chylomicron Remnants
Once the chylomicron has delivered most of its triglyceride content, the remaining, smaller particle is called a chylomicron remnant. The remnant is relatively enriched in cholesterol esters and fat-soluble vitamins because these components were not removed by LPL. It retains the structural ApoB-48 and acquires an apolipoprotein called ApoE from other circulating lipoproteins.
ApoE is the signal protein required for the next and final stage of clearance, which takes place in the liver. The remnants travel to the liver where they must pass through small pores, called fenestrae, to enter the space between the liver cells and the blood vessels. The ApoE on the remnant surface binds to specific receptors on the liver cell membrane, such as the Low-Density Lipoprotein Receptor-related Protein 1 (LRP1).
This binding initiates the internalization of the entire remnant particle into the liver cell. Once inside, the remnant is broken down, and its remaining contents, including cholesterol and vitamins, are processed or repackaged for future use or excretion.
Clinical Relevance
The metabolism of chylomicrons has significant implications for human health and diagnostic testing. A key measure in standard lipid panels is the level of triglycerides in the blood, which is directly related to the presence of chylomicrons and other triglyceride-rich particles. Because chylomicrons are produced only after a meal, their presence in the bloodstream is normally transient, meaning they are typically cleared within hours.
Because of this transient nature, a person is typically asked to fast for 10 to 12 hours before a lipid panel test; fasting ensures chylomicrons from the last meal are cleared, allowing for an accurate baseline measurement of other lipoproteins. When chylomicron clearance is significantly impaired, a condition known as hyperchylomicronemia can occur, where triglyceride levels exceed 1,000 mg/dL.
This severe elevation often results from genetic defects affecting the LPL pathway, such as mutations in the LPL, ApoC-II, or ApoA5 genes. The persistent accumulation of chylomicrons in the blood due to these defects poses a high risk for acute pancreatitis, an inflammation of the pancreas. The detection of very high triglyceride levels is an important clinical marker linked to chylomicron metabolism.