KNOWLEDGE OF DIGESTION AND METABOLISM OF FAT

Reference – Intestinal lipid absorption by Jahangir Iqbal and M.Mahmood Hussain

Am J Physiol Endocrinol Metab. 2009 Jun; 296(6): E1183–E1194.

Published online 2009 Jan 21. doi: 10.1152/ajpendo.90899.2008

The digestion of lipids begins in the oral cavity through exposure to lingual lipases, which are secreted by glands in the tongue to begin the process of digesting triglycerides. Digestion continues in the stomach through the effects of both lingual and gastric enzymes. The stomach is also the major site for the emulsification of dietary fat and fat-soluble vitamins, with peristalsis a major contributing factor. Crude emulsions of lipids enter the duodenum as fine lipid droplets and then mix with bile and pancreatic juice to undergo marked changes in chemical and physical form. Emulsification continues in the duodenum along with hydrolysis and micellization in preparation for absorption across the intestinal wall.

Bile and pancreatic juice provide pancreatic lipase, bile salts, and colipase, which function cooperatively to ensure the efficiency of lipid digestion and absorption. The importance of bile to the efficiency of these processes is indicated by the decreased rate of lipid absorption in humans with bile fistulas. The greatly reduced concentration of bile acid in the duodenum of such individuals suggests that bile salts, although possibly not absolutely necessary for digestion, are essential for the complete absorption of dietary fats. Elevated concentrations of bile salts have been shown to inhibit pancreatic lipase activity in the duodenum. Such inhibition is offset, however, by colipase, which has been shown in vitro to restore pancreatic lipase activity under such circumstances.

It has also been demonstrated in colipase-deficient mice, which when placed on a high-fat diet, developed steatorrhea that was so severe that undigested lipids could be seen in their feces.

Digestion and absorption of TAGs Triacylglycerides

TAG is digested primarily by pancreatic lipase in the upper segment of the jejunum.This process generates a liquid-crystalline interface at the surface of the emulsion particles. The activity of pancreatic lipase on the sn-1 and sn-3 positions of the TAG molecule results in the release of 2-monoacylglycerol (2-MAG) and free fatty acids (FFAs); 2-MAG is the predominant form in which MAG is absorbed from the small intestine. The formation of 2-MAG (and 1-MAG) through isomerization in an aqueous medium occurs more slowly than the uptake of 2-MAG from the small intestine. Further hydrolysis of 1- or 2-MAG by pancreatic lipase results in the formation of glycerol and FFAs; cholesterol esterase can also hydrolyse the acyl group at the sn-2 position to form glycerol and FFAs.

Phospholipids

The predominant PL in the lumen of the small intestine is PC, which is found in mixed micelles that also contain cholesterol and bile salts. The digestion of PLs is carried out primarily by pancreatic phospholipase A2 (pPLA₂) and other lipases secreted by the pancreas in response to food intake.

Vitamin E absorption

Micelle formation is required for the absorption of vitamin E.Pancreatic enzymes may also aid in its absorption; this is suggested by the finding of vitamin E deficiency in patients with cystic fibrosis, who do not secrete pancreatic enzymes.

ASSEMBLY, SECRETION, AND REGULATION OF INTESTINAL LIPOPROTEINS

The major lipoproteins secreted by the intestine are VLDL and chylomicrons. Of these, the chylomicrons are synthesized exclusively in the intestine to transport dietary fat and fat-soluble vitamins into the blood. Chylomicrons are primarily very large, spherical TAG-rich particles that also contain PLs, cholesterol, vitamin E, vitamin A, and protein. The lipoprotein core contains TAG, cholesteryl esters, and fat-soluble vitamins, whereas the surface contains a monolayer of PLs (mainly phosphatidylcholine), free cholesterol, and protein.

DIGESTION AND METABOLISM OF FAT

Reference – Textbook of medical physiology by sembuliṅgam and prema sembuliṅgam, chapter 47, digestion, absorption and metabolism of lipids,jaypee brothers medical publishers, pg no- 292-297

The lipid metabolism begins form the mouth itself by the lingual lipase in saliva. In the stomach, gastric lipase and tributyrase is the lipolytic enzyme, present in gastric juice and acts on the fats.

The major part of the fat metabolism occurs in the small intestine as the substances like the bile salts, pancreatic lipolytic enzymes and intestinal lipase are present in abundance there. By the action of these enzymes the long chain fatty acids are broken down to short chain fatty acids. Finally they are converted into monoglycerides, cholesterol and monoglycerides.

Further assimilation: –

With help of the micelles they get diffused through the intestinal mucosa. In the mucosal cells most of the monoglycerides are converted into triglycerides by re-esterification of fatty acids with 10-12 carbon atoms. Some part of the cholesterol is also esterified.

Triglycerides and cholesterol esters are coated with a layer of protein, cholesterol and phospholipids to form the particles called chylomicrons. These chylomicrons cannot pass through the membrane of the blood capillaries because of the larger size. So, these lipid particles enter the lymph vessels and then are transferred into blood from lymph.

Fatty acids containing less than 10-12 carbon atoms enter the portal blood from mucosal cells and are transported as free fatty acids or unesterified upper part of small intestine. Presence of bile is essential for fat absorption.

Storage of lipids: –

• Lipids are stored in adipose tissue and liver. This stored fat in the adipose tissue is called neutral fat or tissue fat.
• When chylomicrons are travelling through the capillaries of adipose tissue or liver, the enzyme called lipo-protein lipase present in the capillary endothelium hydrolyzes triglycerides of chylomicrons into free fatty acids (FFA) and glycerol.
• FFA and glycerol enter the fat cells of the adipose tissue or liver into triglycerides and stored in these cells. Other contents of chylomicrons such as cholesterol and phospholipids, which are released into the blood combine with protein to form lipo-proteins.
• When other tissues of the body need energy, triglycerides stored in adipose tissue is hydrolysed into FFA and glycerol. FFA is transported to the body tissues through blood.

Utilization of lipids: –

• The FFA from the liver takes part in the Kreb’s cycle with Acetyl CoA, to produce ATP and ketone bodies (Excreted through the kidneys).
• The converted triglycerides and glycerol as glucose and glycogen get utilized by the tissues for cellular metabolism. Also takes part in the Kreb’s cycle to produce ATP.