Lipids absorption

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

ABR Thomson, JM Dietschy. (1981). Intestinal lipid absorption Major extracellular and intracellular events. In LR Johnson, J Christensen, SL Schultz, eds. Physiology of the Gastrointestinal Tract. New York Raven Press, p 1146. 

The targeting of the lipid absorption and metabolism pathways has yielded several promising venues for the treatment of dyslipidemia and insulin resistance. Small molecule inhibitors of MTP have conferred significant reductions in total and LDL cholesterol, as well as plasma TG, in human subjects. While some mechanism-related side effects due to increased hepatic and intraintestinal TG... 

Furthermore, addition of lysine to soy protein markedly increased the rate of lipid absorption and addition of arginine to casein slowed lipid absorption. The slowed absorption of lipids in animals fed soy protein is similar to that reported for soluble fibers such as pectin and guar gum that act to lower serum cholesterol concentrations in a number of animal species, including humans. 

Deficiency of vitamin E is rare it can occur from abnormalities in lipid absorption as well as dietary deficiency. Its deficiency affects the muscular system, causing dystrophy and paralysis and, if the heart is affected, death by myocardial failure. This is probably caused by demyelin-ation of axons due to oxidative damage. Vitamin E is incorporated into chylomicrons within the enterocyte, so that its uptake into cells requires the activity of lipoprotein lipase. 

Faecal bile-acid content was increased in colestimide-supplemented mice consistent with the mode of action of the BAS. In addition, faecal lipid content was raised in treated animals, suggesting reduced lipid absorption, presumably via the lowering of duodenal bile-acid concentration. 

Vitamin A absorption from the small intestine requires dietary fat and pancreatic lipase to break down retinyl esters and bile salts to promote the uptake of retinol and carotene. Drugs, such as mineral oil, neomycin and cholestyramine, that can modify lipid absorption from the gastrointestinal tract can impair vitamin A absorption. The use of oral contraceptives can signihcantly increase plasma vitamin A levels. 

Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S, Rudling M, Myrdal U, Annesi G, Naik S, Meadows N, Quattrone A, Islam SA, Naoumova RP, Angelin B, Infante R, Levy E, Roy CC, Freemont PS, Scott J, Shoulders CC (2003) Mutations in a Sari GTPase of COPII vesicles are associated with lipid absorption disorders. Nat Genet 34 29-31... 

Vitamin E deficiency is almost entirely restricted to premature infants. When observed in adults, it is usually associated with defec tive lipid absorption or transport. The signs of human vitamin E defi ciency include sensitivity of erythrocytes to peroxide, and the appearance of abnormal cellular membranes. 

Factors which decrease availability of the vitamin include (1) biliary obstruction (2) liver damage—cirrhosis, toxins (3) poor food preparation (vitamin is strong-add, alkali, light, and reduction labile) (4) impaired lipid absorption in gut (5) presence of antagonists (6) ingestion of mineral oil (7) sterilization of gut with antibiotics and sulfa drugs and (8) excessive excretion in feces. Availability may be increased by way of storage in the liver and absorption aids, such as bile salts. 

Thomson, A.B.R. et al. (1993) Lipid absorption passing through the unstirred layers, brush-border membrane, and beyondCan. J. Physiol. Pharmacol., 71 531-555. 

Apart from being a diffusional barrier, mucin can also interact with drugs to decrease their bioavailability, as has been shown with tetracycline [106], phenylbutazone, and warfarin [107]. On the other hand, studies in rats showed that binding of some water-soluble drugs to intestinal mucus was essential for their absorption and that damage to the mucus significantly reduced absorption [108], The acidic mucus is essential for lipid absorption and could be important for the diffusion of lipophilic drugs (see below). 

In this light, cholesterol absorption has received intense focus for several decades. Although the various statins lower LDL by decreasing endogenous cholesterol synthesis, another approach to prevent excess cholesterol accumulation is to reduce absorption of dietary cholesterol. Doing so also prevents reabsorption of biliary cholesterol, which can have a major impact on overall cholesterol metabolism since recirculation of biliary cholesterol represents a large portion of the cholesterol that transits through the intestine. For recent reviews on mechanisms of cholesterol and lipid absorption, see ref. (1-3). 

Hui, D. Y., Labonte, E. D., and Howies, P. N. (2008) Development and physiological regulation of intestinal lipid absorption III. Intestinal transporters and cholesterol absorption. Am. J. Physiol. Gastrointest. Liver Physiol. 294, 839-843. 

P. Tso, Intestinal lipid absorption, Physiology of the Gastrointestinal Tract (L. R. Johnson, chief ed.), Raven Press, New York, 1994, pp. 1867-1908. 

Cholesterol also serves as a precursor to other important molecules. Bile acids aid in lipid absorption during digestion. Steroid hormones all derive from cholesterol, including the adrenal hormones that maintain fluid balance Vitamin D, which is an important regulator of calcium status and the male and female sex hormones. Although humans wouldn t survive in one sense or another without cholesterol metabolites, cholesterol brings with it some well-known side effects. Doctors find cholesterol derivatives, being essentially insoluble in water, in the deposits (plaque) that characterize diseased arteries. 

ApoA-IV is an immunologically distinct apolipoprotein of Mr 46,000 (B22, G28, W7). It has been demonstrated in intestinal epithelial cells from fasting subjects and a marked increase has been shown during lipid absorption (G27). About 10-13% of chylomicron apolipoprotein and 24-30% of intestinal VLDL apolipoprotein is apoA-IV. In fasting plasma, 98% of apoA-IV is in the d> 1.21 g/ml fraction and in lipemic plasma 90% is in this fraction, while 10% is associated with triglyceride-rich lipoproteins (G27). Gel permeation chromatography confirmed that in plasma most apoA-IV is free, unassociated with lipoproteins (B22, G27). 

Bile salts are substances derived from sterols, which make up a substantial part of the solid matter in bile and which play a central role in lipid absorption, by virtue of their surface-active properties. The structure and properties of these salts have been reviewed by Haslewood (305) and Heaton (316). Bile salts essentially have molecules of detergent type hydrocarbon, with a fat-dissolving part and a polar, water-attracting part. The fat-dissolving part consists of the bulk of the steroid nucleus. The hydroxyl groups are so distributed that hydration can readily take place the remainder of the molecule will dissolve the fatty phase. Emulsification of fat/water complexes can thus occur easily. The terms bile acid and bile salt are used somewhat interchangeably in the literature. 

Vitamin E, like neutral lipids, requires apoB lipoproteins at every stage of its transport (Fig. 27-2). Dietary vitamin E becomes emulsified in micelles produced during the digestive phase of lipid absorption and permeates the intestinal epithelium, similar to fatty acids and cholesterol. Uptake of vitamin E by enterocytes appears to be concentration dependent. Within intestinal cells, vitamin E is packaged into chylomicrons and secreted into lymph. During blood circulation of chylomicrons, some vitamin E may be released to the tissues as a consequence of partial lipolysis of these particles by endothelial cell-anchored lipoprotein lipase. The rest remains associated with chylomicron remnants. Remnant particles are mainly endocy-tosed by the liver and degraded, resulting in the release of fat-soluble vitamins. 

Reduction of intestinal Reduced biliary excretion of bile salts into the Reduced lipid absorption causing steatorrhoea... 

A major question to address in the future is how structure influences the dynamics of digestion and the signaling processes involved. Armand et al. (1996, 1999) investigated the digestion and lipid absorption from emulsions with different droplet sizes in humans. Healthy subjects received intragastrioally a coarse (10 pm) and a fine (0.7 pm) lipid emulsion of identical composition in random order. Gastric and duodenal aspirates as well as triglyceride appearance in the blood were analyzed. They found an increase in droplet size in the stomach however, the fine emulsion retained droplets... 

Lipoprotein disorders may also result from a variety of intestinal disorders that impede lipid absorption (such as certain inflammatory bowel diseases). Lipid disorders may also occur when there is triglyceride breakdown and shifting of triglyceride stores, as in the lipidemia that may accompany excess lipid breakdown in diabetes. 

---