Chylomicrons, removal from blood

The metabolism of lipid emulsions has long been considered to be similar to that of chylomicrons with intravascular lipolysis by lipoprotein lipase (LPL) being followed by tissue uptake of remnant particles. However, other studies have suggested that lipid emulsions are cleared from blood with less lipolysis than chylomicrons and that a substantial number of emulsions can be cleared as almost intact whole particles by different tissues. The metabolism of lipid emulsions is affected by many factors, including triglyceride (TG) composition. For example, MCT LCT emulsions are cleared faster from blood than pure LCT emulsions. Recently, it was reported that pure FO emulsion particles are removed from blood faster and by different pathways as compared with LCT emulsions. Removal of LCT emulsions is modulated by LPL, apolipoprotein E (apoE), LDL receptor (LDL-R), and lactoferrin-sensitive pathways. In contrast, clearance of FO emulsions relies on LPL to a much lesser extent and is apparently independent of apoE, LDL-R, and lactoferrin-sensitive pathways. It can therefore be noted that the materials selecteds to develop a nanoemulsion composition may not only affect the physicochemical properties and stability of the formulation but may alter significantly the biofate and efficacy of the nanoemulsions. 

LPL found on the endothelial surfaces of the blood capillaries) to produce chylomicron remnants, which are then removed from the circulation by specific remnant receptors located on parenchymal liver cells. VLDLs are secreted by the liver. Following their secretion in blood, VLDLs undergo metabolism in a way... 

When the diet contains more fatty acids than are needed immediately as fuel, they are converted to triacylglycerols in the liver and packaged with specific apolipoproteins into very-low-density lipoprotein (VLDL). Excess carbohydrate in the diet can also be converted to triacylglycerols in the liver and exported as VLDLs (Fig. 21-40a). In addition to triacylglycerols, VLDLs contain some cholesterol and cholesteryl esters, as well as apoB-100, apoC-I, apoC-II, apoC-III, and apo-E (Table 21-3). These lipoproteins are transported in the blood from the liver to muscle and adipose tissue, where activation of lipoprotein lipase by apoC-II causes the release of free fatty acids from the VLDL triacylglycerols. Adipocytes take up these fatty acids, reconvert them to triacylglycerols, and store the products in intracellular lipid droplets myocytes, in contrast, primarily oxidize the fatty acids to supply energy. Most VLDL remnants are removed from the circulation by hepatocytes. The uptake, like that for chylomicrons, is... 

Increased triacylglycerol synthesis Triacylglycerol synthesis is favored because fatty acyl CoA is available both from de rxxo synthesis from acetyl CoA and from hydrolysis of the triacylglycerol component of chylomicron remnants removed from Ihe blood by hepatocytes (see p. 176). Glycerol 3-phosphate, Ihe... 

The chylomicrons are stabilized by adsorbed lipoprotein and phospholipids. The lymph enters the bloodstream at the juncture of the thoracic duct and the subclavian vein. This dietary fat is largely removed from the blood by the cells of adipose tissue. 

It is now generally agreed that in these subjects hyperlipemia is caused by defective removal from the blood of dietary chylomicrons (Havel and Gordon 1960, Fredrickson and Lees 1965), the half life of which is usually markedly... 

They can be synthesized by the gut, following the absorption of hydrolyzed dietary lipid. They are combined with small amounts of protein, cholesterol and phospholipid to form chylomicrons. These are removed from the blood, mainly by adipose tissue. An enzyme, lipoprotein lipase is responsible for this hydrolysis of the chylomicron triglycerides. The free fatty acids liberated by these processes are resynthesized into triglycerides by the adipose tissue and stored. 

As the lipoproteins are depleted of triacylglycerol, the particles become smaller. Some of the surface molecules (apoproteins, phospholipids) are transferred to HDL. In the rat, remnants that result from chylomicron catabolism are removed by the liver. The uptake of remnant VLDL also occurs, but much of the triacylglycerol is further degraded by lipoprotein lipase to give the intermediate-density lipoprotein (IDL). This particle is converted into LDL via the action of lipoprotein lipase and enriched in cholesteryl ester via transfer from HDL by the cholesteryl ester transfer protein. The half-life for clearance of chylomicrons from plasma of humans is 4-5 min. Patients with the inherited disease, lipoprotein lipase deficiency, clear chylomicrons from the plasma very slowly. When on a normal diet, the blood from these patients looks like tomato soup. A very-low-fat diet greatly relieves this problem. 

Atherosclerosis and Plasma Lipids - Lipoprotein lipases play a critical role in the metabolism of lipoproteins and thus may be involved in athero-genesis. Hypercholesterolemia in the cholesterol-fed rabbit was attributed to the accumulation of chylomicron remnants, which may be formed on the aorta wall by lipoprotein lipase and deposited in the deep layers of the arterial wall without prior release into the blood stream.13 On this basis, cholesterol-rich lipoproteins in plasma may be the product rather than the cause of the atherogenic process. However, the defect in Type III hyperlipoproteinemia (broad- disease) may be ineffective removal of chylomicron remnant particles from the arterial wall,11 due to a failure of the liver to recognize such particles.15... 

Type I—A relatively rare inherited deficiency of either lipoprotein lipase activity or the lipoprotein lipase-activating protein apo C-11. This results in the inability to effectively remove chylomicrons and VLDL triglycerides from the blood. 

After entry in the blood stream the chylomicrons are hydrolyzed by the endothelial-bound lipoprotein lipase with apo C-I as a co-factor, allowing the delivery of free FAs to muscle and adipose tissue. The chylomicron remnants are rapidly taken up into the liver via especial receptor. ApoE is the moiety required for rapid hepatic removal. Its activity is inhibited by C apolipoproteins, especially apoC-I. The liver utilizes the exogenous fat and can release surplus lipids via VLDL into the blood. The VLDL is another substrate for lipoprotein lipase. The remaining VLDL remnants can either be taken up into the liver or are hydrolyzed to LDL. These last delivers cholesterol to all body cells via its receptor [136]. Moreover other type of lipoprotein denominated as high-density protein (HDL) is an important scavenger of surplus cholesterol transporting it from cell membranes to the liver, where it is degraded or converted into biliary salts, an then eliminated by the entero-hepatic cycle [137]. 

Sites of initial removal of chylomicron triglyceride fatty acids from the blood. J. din. 

Nestel, P. j., R. j. Havel, and A. Bezman Sites of initial removal of chylomicron triglyceride fatty acids from the blood. J. din. Invest. 41, 1915 (1962). 

Pre-fi lipoproteins (ve low density lipoproteins). These also are composed mainly of triglyceride but have higher proportions of cholesterol, phospholipid and protein than chylomicrons. Pre-j3-lipoproteins transport endogenously synthesized triglycerides in the blood. Removal of triglycerides from pre-j5-lipoproteins results in the formation of -lipoproteins. 

This condition results in inability to remove chylomicrons from the blood. It presents in childhood with eruptive xanthomas, lipaemia retinalis, retinal vein thrombosis, pancreatitis and hepatosplenomegaly... 

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