Blood Chylomicrons

Chylomicroiis leave the lymph and enter the peripheral blood where the thoracic duct joins the left subdavian vein, thus initially bypassing the hver. After a high-fat meal, chylomicrons cause serum to become turbid or milky. While in the blood, chylomicrons acquire apoC-II and apoE from HDL particles. 

It is well known that dietary fat is not absorbed from the intestine unless it has been subjected to the action of pancreatic lipase [1], Previously, we found that basic proteins such as protamines, histones and purothionine inhibited the hydrolysis of triolein emulsified with phosphatidylcholine [2], The inhibition of hydrolysis of dietary fat may cause a decrease or delay in the intestinal absorption of fat and reduce blood chylomicron levels, an excess of which is known to induce obesity [3], Therefore, there was a possibility that inhibitory substances toward pancreatic lipase activity may prevent the onset of obesity induced by feeding a high fat diet to mice. Recently, we found that natural products such as tea saponin, platycodi radix saponin, chitin-chitosan and chondroitin sulfate inhibited the pancreatic lipase activity. In the following section, the anti-obesity effects of these natural products will be described in detail. 

In summary, the nature of the chylomicron protein is undetermined. It is possible that during fat absorption a protein is formed in the cells of intestinal mucosa, perhaps in the ribosomal fraction, at the same time that triglyceride synthesis occurs. The newly formed protein or proteins may be unrelated to plasma lipoproteins and perhaps constitute the structural chylomicron protein corrresponding to the unidentified fraction in the studies by Rodbell et al. (1 9) and Scanu and Page (1959). Upon entering the lymph and then the blood, chylomicrons may acquire additional protein at the expense of circulating hpoproteins of hepatic derivation (Scanu and Page, 1959). 

Fat, including cholesterol, absorbed from the diet is insoluble in the water-based medium of the blood. To enable transport through the blood system, the various fat components are incorporated into particles called lipoproteins (for reviews on lipoprotein metabolism, see Grundy, 1983 Mahley and Innerarity, 1983). Lipoproteins consist of a lipid core of triglyceride and cholesterol ester with a surface of mainly phospholipid and protein (referred to as apolipoprotein), plus some free cholesterol. The different apolipoproteins present function to regulate lipoprotein metabolism (for review on apolipoproteins, see Mahley et al., 1984). The cholesterol in lipoproteins is mainly transported as cholesterol ester. There are four main lipoprotein fractions found in the blood chylomicrons, very-low density lipoprotein (VLDL), low density Upopro-tein (LDL), and high density lipoprotein (HDL). 

The clearance of labeled chylomicrons from the blood is rapid, the half-time of disappearance being under 1 hour in humans. Larger particles are catabolized more quickly than smaller ones. Fatty acids originating from chylomicron triacylglycerol are delivered mainly to adipose tissue, heart, and muscle (80%), while about 20% goes to the liver. However, the liver does not metabolize native chylomicrons or VLDL significantly thus, the fatty acids in the liver must be secondary to their metabolism in extrahepatic tissues. 

Figure 25-2. The formation and secretion of (A) chylomicrons by an intestinal cell and (B) very low density lipoproteins by a hepatic cell. (RER, rough endoplasmic reticulum SER, smooth endoplasmic reticulum G, Golgi apparatus N, nucleus C, chylomicrons VLDL, very low density lipoproteins E, endothelium SD, space of Disse, containing blood plasma.) Apolipoprotein B, synthesized in the RER, is incorporated into lipoproteins in the SER, the main site of synthesis of triacylglycerol. After addition of carbohydrate residues in G, they are released from the cell by reverse pinocytosis. Chylomicrons pass into the lymphatic system. VLDL are secreted into the space of Disse and then into the hepatic sinusoids through fenestrae in the endothelial lining.

Hypolipoproteinemias Abetaiipoproteinemia No chylomicrons, VLDL, or LDL are formed because of defect in the loading of apo B with lipid. Rare blood acylglycerols low intestine and liver accumulate acylglycerols. Intestinal malabsorption. Early death avoidable by administration of large doses of fat-soluble vitamins, particularly vitamin E. 

Heart Pumping of blood Aerobic pathways, eg, P-oxidation and citric acid cycle Free fatty acids, lactate, ketone bodies, VLDL and chylomicron triacylglycerol, some glucose Lipoprotein lipase. Respiratory chain well developed. 

A schematic representation of the metabolism of lipoproteins is shown in Fig. 12 [170]. Chylomicrons are synthesized and secreted by the small intestine. They are hydrolyzed in blood by the enzyme lipoprotein lipase... 

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... 

Chylomicrons leave the absorptive cell by way of exocytosis. Because they are unable to cross the basement membrane of the blood capillaries, the chylomicrons enter the lacteals, which are part of the lymphatic system. The vessels of the lymphatic system converge to form the thoracic duct that drains into the venous system near the heart. Therefore, unlike products of carbohydrate and protein digestion that are transported directly to the liver by way of the hepatic portal vein, absorbed lipids are diluted in the blood... 

Hyperlipoproteinemia, Type V. This pathology is manifested by increased con-tents of chylomicrons, pre-P-lipoproteins, triglycerides, and cholesterol in the patients blood plasma. 

Lipoprotein (LPLase) is required for the metabolism of both chylomicrons and VLDL. This enzyme is induced by insulin and transported to the luminal surface of capillary endothelium where it is in direct contact with the blood. Lipoprotein lipase hydrolyzes the fiitty adds from triglycerides carried by ch)4oinicrons and VLDL and is activated by apoC-II. 

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. 

The metabolism of VLDL is very similar to that of chylomicrons, the major difference being that VLDL are assembled in hepatocytes to transport triglyceride containing fatty acids newly synthesized from excess glucose, or retrieved from the chylomicron remnants, to adipose tissue and musde. ApoB-100 is added in the hepatocytes to mediate release into the blood. Like chylomicrons, VLDL acquire apoC-II and apoE from HDL in the blood, and are metabolized by lipoprotein lipase in adipose tissue and musde. 

HDL is synthesized in the liver and intestines and released as dense protein-rich particles into the blood. They contain apoA-1 used for cholesterol recovery from fatty streaks in the blood vessels. HDL also carry apoE and apoC-11, but those apoproteins are primarily to donate temporarily to chylomicrons and VLDL. 

Figure 4.4 Diagram of the structure of a villus. Most of the absorbed materials enter the blood vessel, but chylomicrons enter the lymph in the lacteals.

Figure 4.13 Uptake of bile acids in the jejunum. Bile adds (BA) and cholesterol (C) are secreted from the liver, via the bile, into the duodenum. Cholesterol is transported back into the blood, from the enterocyte, within chylomicrons. The latter enter the lymphatic system (i.e. the lacteals). Bile acids are absorbed from the jejunum into the hepatic portal vein for re-uptake into the liver.

Figure 7.4 Fate of triacylglycerol that is present in fuel blood after secretion by the intestine. The dietary triacylglycerol in the intestine is hydrolysed to long-chain fatty acids and monoacyl-glycerol, both of which are taken up by the enterocytes in which they are then re-esterified. The triacylglycerol is released in the form of chylomicrons into the blood, from where it is hydrolysed to fatty acids and glycerol by the enzyme lipoprotein lipase in specific tissues (Figure 7.3). The fatty acids are taken up by adipocytes, muscle fibres and secretory cells in the mammary gland.

The packaging of triacylglycerol into chylomicrons or VLDL provides an effective mass-transport system for fat. On a normal Western diet, approximately 400 g of triacylglycerol is transported through the blood each day. Since these two particles cannot cross the capillaries, their triacylglycerol is hydrolysed by lipoprotein lipase on the luminal surface of the capillaries (see above). Most of the fatty acids released by the lipase are taken up by the cells in which the lipase is catalytically active. Thus the fate of the fatty acid in the triacylglycerol in the blood depends upon which tissue possesses a catalytically active lipoprotein lipase. Three conditions are described (Figure 7.23) ... 

Figure 7.23 Fate of blood triacylglycerol (in the chylomicrons and VLDL) in three conditions role of changes in activity of lipoprotein lipase in directing the uptake of fatty acids. It is primarily the activity of Lipoprotein lipase that directs which tissue/organ takes up the fatty acids from the blood triacylglycerol. The abbreviation LPLT indicates a change to a higher activity of lipoprotein lipase LPL-i indicates a change to a lower activity of lipoprotein lipase. The broadness of the arrow indicates the dominant direction of the fate of the fatty acid.

An interesting additional point is that during trauma the cytokine, tumour necrosis factor, results in a decrease in lipase activity in adipose and other tissues, so that there is an increase in the level of VLDL and chylomicrons in the blood. The significance of this is unclear but it may be that pathogens in the blood are adsorbed onto the emulsion of VLDL or chylomicrons which reduces the risk of adsorption of the pathogen onto the surface of a cell, which is necessary for the pathogen to enter the ceU. This localisation also aids attack by antibodies (Chapter 17). 

Triacylglycerol in the forms of chylomicrons or very low density lipoproteins constitutes the mass transport system of fat in the blood. Excessive levels, particularly of VLDL, can give rise to various pathological problems which are grouped together under the title lipoproteinaemias and are discussed in Chapter 11 (Appendix 11.9). 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

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