Lipid absorption simplified

Absorption of Lipids

• Glycerol, short and medium-chain fatty acids (chain lengths less than 14 carbons) are directly absorbed from the intestinal lumen into the portal vein and taken to the liver for further utilization.
• Long-chain fatty acids, free cholesterol, and β- acyl glycerol together with bile salts form mixed micelles.

Micelles

• Micelles are disk-shaped clusters of amphipathic lipids that coalesce with their hydrophobic groups on the inside and their hydrophilic groups on the outside of clusters (figure-1).
•  Mixed micelles are soluble in the aqueous environment of the intestinal lumen
•  Micelles are about 200 times smaller than emulsion droplets (4-7nm versus 1µm for emulsion droplets).
• Micelles are necessary because they transport the poorly soluble monoglycerides and fatty acids to the surface of the enterocyte where they can be absorbed.
•  The micelles approach the brush border membrane of the enterocytes. This membrane is separated from the liquid contents of the intestinal lumen by an unstirred water layer that mixes poorly with the bulk fluid (figure-2).
• The hydrophilic surface of the micelles facilitates the transport of the hydrophobic lipids through the unstirred water layer to the brush border where they are absorbed.

Figure-1- micelles are disk-shaped clusters of amphipathic lipids that coalesce with their hydrophobic groups on the inside and hydrophilic groups on the outside of the clusters.

• Micelles constantly break  down and re-form
• It is the monoglycerides and fatty acids that are free in the solution that are absorbed, NOT the micelles.
• Because of their nonpolar nature, monoglycerides and fatty acids can just diffuse across the plasma membrane of the enterocyte. 
• Some absorption may be facilitated by specific transport proteins

Figure-2- Absorption of lipids contained in mixed micelles by intestinal mucosal cell

Cholesterol absorption

Some of the cholesterol in the small intestine is dietary cholesterol, and some are poured there by the liver, arriving via the bile (figure-3). Of the total cholesterol that passes through the small intestine, only half is typically absorbed, and the rest is eliminated in the feces. Thus, cholesterol in the bile is an example of a substance that is targeted for excretion via the digestive tract.

Figure-3- Absorption, and excretion of cholesterol

Clinical Significance

• The drug ezetimibe blocks a protein that specifically mediates cholesterol transport across the apical plasma membrane of enterocytes.
• Ezetimibe has been shown to be effective at reducing levels of LDL cholesterol, particularly when combined with a statin, a drug that inhibits cholesterol synthesis in the liver.

 Lipid Malabsorption(Steatorrhea)

• Lipid malabsorption results in increased lipids including fat-soluble vitamins A, D E and K in the feces.
• The cause may be pancreatic insufficiency, including cystic fibrosis, chronic diseases of pancreas or surgical removal of the pancreas
• Shortened bowel, Celiac diseases, sprue or Crohn’s disease
• Maybe bile duct obstruction due to gall stones, the tumor of head of the pancreas, enlarged lymph nodes, etc.
• Milk and coconut oil are used therapeutically since they contain medium-chain fatty acids.

Secretion of lipids from enterocytes

• Once inside the enterocyte, monoglycerides and fatty acids are re-synthesized into TAG.
• Lysophospholipids are recycled to form phospholipids.
• Cholesterol is re acylated to form Cholesteryl esters
• Long-chain fatty acids are used for esterification to form TGs, phospholipids and cholesteryl esters.
• Short and medium-chain fatty acids are released into the portal circulation and are carried by serum albumin to the liver.
• The TGs are packaged, along with cholesterol and fat-soluble vitamins, into chylomicrons.
• Chylomicrons are lipoproteins, special particles that are designed for the transport of lipids in the circulation. 
• Chylomicrons are released by exocytosis at the basolateral surface of the enterocytes. Because they are particles, they are too large to enter typical capillaries.
• Instead, they enter lacteals, lymphatic capillaries that poke up into the center of each villus.
• Chylomicrons then flow into the circulation via lymphatic vessels.

Figure-3-Within the intestinal epithelium, the products of lipid digestion and absorption are repacked as chylomicrons for transportation to peripheral cells.

 Structure of Chylomicron

• Size: 0.1–1 µm
• Average composition (figure-4)
• TG (84%)
• Cholesterol(2%)
• Ester Cholesterol (4%)
• Phospholipid (8%)
• Apo lipoproteins (2%)

Figure-4- General structure of a lipoprotein

The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules. These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane. The protein moiety of lipoprotein is known as an apolipoprotein or apoprotein, (B48).

Transport and Utilization of chylomicrons

The clearance of chylomicrons from the blood is rapid, the half-time of disappearance being under 1 hour in humans. Fatty acids originating from chylomicron triacylglycerol are delivered mainly to adipose tissue, heart, and muscle (80%), while about 20% goes to the liver. Triacylglycerol is hydrolyzed progressively through a diacylglycerol to a monoacylglycerol and finally to free fatty acids plus glycerol. Some of the released free fatty acids return to the circulation, attached to albumin, but the bulk is transported into the tissues. The resulting chylomicron remnants, rich in cholesterol are taken up by the liver by receptor-mediated endocytosis.

 Clinical significance of Chylomicron synthesis and utilization

• Defective synthesis- Due to deficiency of apo-B 48 protein. The triglyceride may accumulate in intestinal cells.
• Chyluria- Due to an abnormal connection between the urinary tract and lymphatic drainage system of the intestines, forming Chylous fistula. Characterized by the passage of Milky urine.
• Chylothorax- There is an abnormal connection between pleural space and the lymphatic drainage of the small intestine resulting in accumulation of lymph in the pleural cavity giving Milky pleural effusion.

 Summary of lipid digestion and Absorption

Figure-6- Summary of digestion and absorption of lipids

Chylomicrons deliver absorbed TAG to the body’s cells. TAG in chylomicrons and other lipoproteins are hydrolyzed by lipoprotein lipase, an enzyme that is found in capillary endothelial cells. Monoglycerides and fatty acids released from the digestion of TAG then diffuse into cells.