K. Normal Fat Absorption

Fat has nine calories per gram whereas carbohydrate and protein have only 4. In countries with a standard of living like ours, fat constitutes almost half the caloric intake. Well over 95% of fat ingested is normally absorbed. In intestinal mucosal disease, fat is the most common nutrient whose absorption is impaired.

Figure 10

Overview of the fatty problem Dietary fat is mostly long-chain triglyceride which is extremely insoluble in water (nonpolar). The human body is composed mostly of water, but its cell barriers are mostly lipid. Therefore, fat absorption is essentially a transport problem involving movement from water compartments through lipid membranes to water again. Specifically, the problem is how to dissolve or disperse fat widely in the water of the intestinal lumen and then facilitate its efficient transport to and through the absorptive cell’s lipid membrane. Once it is inside the cell, it has to be packaged in a multimolecular form (chylomicrons) which can be carried safely in blood water as a finely dispersed stable emulsion.

What follows is a highly simplified account of a very complex, poorly understood process. Biochemists and physiologists are providing new insights into the physiochemical characteristics of intestinal contents, and into derangements in function of small intestinal absorptive cells. These insights may prove useful in understanding normal fat absorption and the pathogenesis of fat malabsorption.

An approach to fat absorption which has proven useful to us over the years is to divide the various phases of fat absorption anatomically into successive “way-stations” along the absorptive pathway: the stomach, the duodenojejunal lumen, absorptive cells, lamina propria, and lymphatics, as well as the ileum.

1. Stomach

Metered emptying

Gastric lipase Gastric contractions emulsify fats with the aid of food proteins and lecithins. Relatively little digestion of fat occurs in the adult stomach. However, gastric lipase activity may be of importance in the newborn and in adults with pancreatic insufficiency. The normal stomach delivers the meal gradually over a period of several hours to the duodenal lumen.

2. Duodenojejunum – Lumen

As the food digests, fatty acids and amino acids stimulate release of CCK and secretin from the duodenal mucosa which assure a continuous flow of bile and pancreatic juice for optimal luminal digestion. CCK- and secretin-secreting cells are most prevalent in the upper third of the small gut.

a. Emulsification and Triglyceride Digestion:

Lecithins in food help to stabilize gastric emulsions. To increase lipolysis the area of the oil-water interface must be expanded. This is accomplished by emulsification, a process of dispersing the lipid into innumerable several-micron-diameter fat droplets within the watery luminal contents which gives it a milky appearance. Chewing and the churning action of the gastric antrum and small bowel in the presence of emulsifying agents from food and bile (proteins, lecithins and bile salts) emulsifies the triglyceride. Pancreatic lipase with colipase acts at the oil-water interface to hydrolyze (lipolysis) insoluble, nonpolar, triglyceride to somewhat soluble free fatty acids and poorly soluble monoglycerides. Pancreatic phospholipase hydrolyzes lecithin to lysolecithin and fatty acid.

Figure 11

b. Aqueous Dispersion:

Emulsification increases oil-water interface

The CMC With the aid of the detergent action of bile salts, a whole spectrum of sizes of multimolecular particles are formed (<200 Ã… diameter micelles and > 500 Ã… diameter vesicular aggregates) composed of fatty acids, lecithins and monoglycerides. Remember that the emulsified particles within the intestinal lumen are 100,000 times larger. Emulsification promotes lipolysis by increasing the area of oil-water interface where lipolysis occurs but it does not provide adequate dispersion in luminal water to promote absorption. Moderate centrifugation of the luminal contents after a fatty meal causes the larger emulsion particles to float to the top of the centrifuge tube into an oil phase, while the spectrum of micelles and liposomes remains widely dispersed within the aqueous phase in the rest of the centrifuge tube (Figure 12). The large emulsified particles in the oil phase are made up of undigested triglyceride with some of the products of digestion coating the particles and dissolved within them. An adequate concentration of conjugated bile salts (critical micellar concentration – CMC) and a pH buffered to near neutrality is necessary for formation of micelles.

Figure 12

Lipids can be solubilized inside mixed micelles

Mixed micelles carry lipids across the unstirred water layer to the enterocytes The molecules of the lipid aggregates are so oriented that their polar groups face the surrounding watery medium which enables them to be widely dispersed or “dissolved” within the luminal contents. Their nonpolar interiors can dissolve lipids such as cholesterol and the fat-soluble vitamins (D, A, K and E). Thus these lipid aggregates are vehicles to transport water-insoluble molecules (lipids) in the watery luminal contents, as well as carry them through the unstirred water layer to the microvillous membrane of the absorptive cell, through which the lipid molecules are absorbed.

Recycling of bile salts across the unstirred water layer The ionized, conjugated bile salts are very poorly absorbed by duodenojejunal mucosa, and return to the bulk phase of intestinal contents to form more mixed micelles.

3. Duodenojejunum – Mucosa

Fatty acid binding proteins in the cytosol of the enterocytes facilitate the transfer of free fatty acids (FFA) from the apical membrane to the smooth endoplasmic reticulum where they are synthesized to triglycerides, which are absorbed via the lacteals (lymphatics). Short-chain fatty acids are absorbed directly into the lymph stream. Triglyceride synthesis and absorption into the lymph maintains a downhill concentration gradient of FFA from lumen to within the cell.

Composition of chylomicrons The absorptive cell manufactures lipoprotein lipid particles for export into the blood continuously, both fasting (VLDL) and after a fatty meal (VLDL and chylomicrons). The particles manufactured during the fasting state are called the very low density lipoprotein particles (VLDL), and they are much smaller (average – 750 Ã…) than the predominant postprandial lipoprotein particles which are called chylomicrons (1,500 5,000 Ã…). (Remember 10,000 Ã… = 1 µm and 7.5 µm is the average diameter of a red cell). The source of the VLDL is the fasting luminal contents which contain fatty acids split from biliary lecithin by pancreatic phospholipase A; these fatty acids are synthesized into triglyceride within the absorptive cell where small amounts of apoprotein B (essential for fat transport) cholesterol, cholesterol ester, and phospholipid are added. When a meal of triglyceride (TG) is digested in the lumen, many more molecules of fatty acid and monoglyceride enter the cell and are resynthesized into triglyceride. More VLDL, as well as fat particles of progressively larger size, are now manufactured. Some believe that chylomicrons merely are TG-expanded versions of the VLDL, which are its precursors.

Figure 13

Chylomicrons and VLDL leave the absorptive cells, probably by reverse pinocytosis and travel through the extracellular portion of the lamina propria to enter the lacteals and eventually reach the systemic circulation.

Figure 14

The ileal back-up Normally all fat absorption occurs within the duodenum and jejunum. If for any reason jejunal absorption is impaired, the ileum serves as the backup system for lipid in addition to retrieving bile salts.