Cholesterol lymph

The half-life of liposomes administered in the blood stream is affected by the composition, size, charge, and fluidity. Liposomes with a small size or with a rigid lipid bilayer have a longer half-life (38 9). Large liposomes administered iv tend to accumulate at a lymph node near the injected site. This tendency can be useful for preventing metastases. Liposomes which pass through the lymph node have a tendency to accumulate in the RES, such as the liver and spleen (40,41). The disposition of liposomes is altered by the dose of liposomes as well as size or lipid composition of liposomes. Cholesterol rich liposomes are cleared slower due to... 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

Chylomicrons are assembled from dietary triglyceride (containing predominantly the longer-chain fatty adds) and cholesterol esters by intestinal epithelial cells. The core lipid is surrounded by phospholipids similar to those found in cell membranes, which increase the solubility of chylomicrons in lymph and blood. ApoB-48 is attached and required for release from the epithelial cells into the lymphatics. 

Figure 4 Transverse scan of axillary and subscapular lymph nodes in a rabbit 5 min postinjection of Gd-containing liposomes. Liposomes (egg lecithin cholesterol Gd-poly-NGPE = 70 25 5, 20 mg total lipid) were injected subcutaneously into the forepaw of anesthesized rabbit in 0.5 mL of HEPES-buffered saUne. Images were acquired by using a 1.5 Tesla GE Signa MRl scanner operated at fat suppression mode and Tj-weighted pulse sequence [16].

Lipoprotein metabolism. Entero-cytes release absorbed lipids in the form of triglyceride-rich chylomicrons. Bypassing the liver, these enter the circulation mainly via the lymph and are hydrolyzed by extrahepatic endothelial lipoprotein lipases to liberate fatty acids. The remnant particles move on into liver cells and supply these with cholesterol of dietary origin. 

The food components resorbed by the epithelial cells of the intestinal wall in the region of the jejunum and ileum are transported directly to the liver via the portal vein. Fats, cholesterol, and lipid-soluble vitamins are exceptions. These are first released by the enterocytes in the form of chylomicrons (see p. 278) into the lymph system, and only reach the blood via the thoracic duct. 

In the mucosal cells, long-chain fatty acids are resynthesized by an ATP-dependent ligase [5] to form acyl-CoA and then triacylglycerols (fats see p. 170). The fats are released into the lymph in the form of chylomicrons (see p. 278) and, bypassing the liver, are deposited in the thoracic duct—i. e., the blood system. Cholesterol also follows this route. 

The plasma membrane, a phospholipid bilayer in which cholesterol and protein molecules are embedded. The bottom layer, which faces the cytoplasm, has a slightly different phospholipid composition from that of the top layer, which faces the external medium. While phospholipid molecules can readily exchange laterally within their own layer, random exchange across the bilayer is rare. Both globular and helical kinds of protein traverse the bilayer. Cholesterol molecules tend to keep the tails of the phospholipids relatively fixed and orderly in the regions closest to the hydrophilic heads the parts of the tails closer to the core of the membrane move about freely. This model is not believed to apply to blood or lymph capillaries. (Reprinted with permission from Bretscher MS. The molecules of the cell membrane. Sci Am 1985 253 104. Copyright 1985 by Scientific American, Inc. All rights reserved.)... 

Part of the cholesterol newly synthesized in the liver is excreted into bile in a free non-esterified state (in constant, amount). Cholesteiol in bile is normally complexed with bile salts to form soluble cholic acids, Free cholesterol is not readily soluble and with bile stasis or decreased bile salt concentration may precipitate as gallstones. Most common gallstones are built of alternating layers of cholesterol and calcium bilirubin and consist mainly (80-90%) of cholesterol. Normally. 80% of hepatic cholesterol arising from blood or lymph is metabolized to cholic acids and is eventually excreted into the bile in the form of bile salts. 

FIG. 2 Transport of cholesterol (CHOL) and plant sterols (PS) in the enterocyte. CHOL, PS, and other lipids are solubilized in micelles that deliver the lipids to the brush border membrane. CHOL and PS are transported into the enterocyte by NPC1L1. Nearly all of the PS are redirected back to the intestinal lumen by the transporters ABCG5 and ABCG8. The extent to which CHOL is transported by ABCG5 and ABCG8 is not known. CHOL within the enterocyte is packaged into lipoproteins (chylomicrons) and secreted into lymph and eventually the bloodstream for transport to the liver. 

Despite these variables, it appears that the primary attribute of soluble fibers that inhibit cholesterol absorption is the ability to form a viscous matrix when hydrated. Many water-soluble fibers become viscous in the small intestine (Eastwood and Morris, 1992). It is believed that increased viscosity impedes the movement of cholesterol, bile acids, and other lipids and hinders micelle formation, thus reducing cholesterol absorption and promoting cholesterol excretion from the body. Consumption of viscous fibers was shown to increase the thickness of the unstirred water layer in humans (Flourie et al., 1984 Johnson and Gee, 1981) and reduce the amount of cholesterol appearing in the lymph of cannulated rats (Ikeda et al., 1989b Vahouny et al., 1988). Turley et al. (1991, 1994) reported that... 

Feldman et al. (1979a,b) were the first to demonstrate a reduction in cholesterol absorption due to dietary stearic acid in rats. The investigators used three different methods to quantify cholesterol absorption (i.e., plasma isotope ratio method, fecal dual isotope method, and lymph duct can-nulation), and in each case absorption was significantly decreased by stearic acid. Other studies using lymph duct cannulated rats fed stearic acid-enriched diets showed significant reductions in cholesterol absorption (Chen et al., 1989 Ikeda et al., 1994). Using a more realistic dietary approach,... 

TG are derived directly from the diet and secreted from the intestines (primarily by way of the lymph) as CM and TRL or synthesized into VLDL in the liver. The net transport of TG is therefore from the intestines and the liver to skeletal and cardiac muscle or to adipose tissue for storage. Cholesterol is used for membrane synthesis and steroid production and is primarily synthesized in extrahepatic tissues. It is continuously transported between the liver, intestines, and extrahepatic tissues, but the net transport of cholesterol is from the extrahepatic tissues to the liver and intestines from where it is eliminated. 

In summary, triacylglycerols from the diet are digested by lipase and associate with bile salts into mixed micelles. The free fatty acids are absorbed by the cells of the small intestine, from which they are transported via the lymph system to the liver. From the liver, they are released as apolipoproteins in the circulation, carrying fatty acids and cholesterol to the cells throughout the body. 

Reichl et al. have measured the concentration of LDL cholesterol in lymph, and compared it with that in plasma (R9). Knowing the concentration of LDL cholesterol above which maximum suppression of B-100,E receptors occurs in cells in tissue culture, it has been calculated that LDL levels in interstitial fluids would be sufficient to occupy LDL receptor sites in body cells if the plasma LDL-cholesterol concentration was only 25 mg/100 ml (R9). LDL cholesterol in industrialized man is at least four times that level, that is, well above the level at which maximum suppression of most LDL receptors would be expected to occur. 

K16. Klein, R. L., and Rudel, L. L., Effect of dietary cholesterol level on the composition of thoracic duct lymph lipoproteins isolated from nonhuman primates. ]. Lipid Res. 24, 357-367 (1983). 

Vine, D.F., Croft, K.D., Beilin, L.J., Mamo, J.C.L. 1997. Absorption of dietary cholesterol oxidation products and incorporation into rat lymph chylomicrons. Lipids 32, 887-893. 

Lymphadenopathy is most often not clinically manifested however, bright yellow plaques and a cholesterol ester content 100-fold higher than normal have been documented for both normal-size and enlarged lymph nodes in Tangier patients. Biopsies of bone marrow and the affected tissues have revealed many foam cells that are smaller than those observed in lipid storage diseases. In addition, these cells contain sudanophilic deposits which are not membrane-bound, as is the case for lysosomal storage diseases. Foam cells have also been found in otherwise normal skin, ureters, renal pelvises, tunica albuginea (white fibrous capsule) of testicles, mitral and tricuspid valves, and aorta, coronary, and pulmonary arteries. 

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. 

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