Chylomicrons formation

Type V hyperlipoproteinemia requires stringent restriction of dietary fat intake. Drug therapy with fibrates or niacin is indicated if the response to diet alone is inadequate. Medium-chain triglycerides, which are absorbed without chylomicron formation, may be used as a dietary supplement for caloric intake if needed for both types I and V. 

B-48 2152 241 Intestine Chylomicron formation ligand for liver chylomicron receptor... 

Log P is not the only parameter to determine the ability of a molecule to be transported via the lymph. As the lymphatic absorption is associated with chylomicron formation, which is composed mainly from a triglycerides core (85%-92%) [62], the solubility of the prodrug in triglycerides is an important indicator for lymphatic transport capacity potential. Charman and Stella suggested that solubility in triglycerides of at least 50 mg/mL is required before lymphatic transport is likely to occur [63],... 

When rats were fed a high olive oil diet the apoA-IV concentration in lipoprotein-free plasma was increased (compared with rats on a control diet). When cholesterol was added to the diet the lipoprotein-free plasma apoA-IV concentration was higher still, but the HDL apoA-IV was decreased (D9). It is possible, therefore, that apoA-IV metabolism is related to chylomicron formation or metabolism, or cholesterol metabolism, but its significance in man is unknown. 

Figure 22.5. Chylomicron Formation. Free fatty acids and monoacylglycerols are absorbed by intestinal epithelial cells. Triacylglycerols are resynthesized and packaged with other lipids and apoprotein B-48 to form chylomicrons, which are then released into the lymph system.

C. The pancreas produces bicarbonate (which neutralizes stomach acid) and digestive enzymes (including the lipase that degrades dietary lipids). Decreased bicarbonate will lead to a decrease of intestinal pH. Decreased digestion of dietary triacylglycerols will lead to formation of fewer bile salt micelles. Intestinal cells will have less substrate for chylomicron formation, and less fat-soluble vitamins will be absorbed. More dietary fat will be excreted in the feces. 

After its absorption into the intestinal mucosal cell, cholesterol, together with triglycerides, phospholipids, and a number of specific apoproteins, is assembled into a large lipoprotein called the chylomicron (see later section on lipoprotein metabolism, exogenous pathway). One apoprotein component known as apolipoprotein (apo) B-48 is vital to the formation of chylomicrons, and in people with a rare deficiency of apo B-48 synthesis, chylomicron formation, and consequently cholesterol and fat absorption, is severely impaired. Chylomicrons enter the lymphatics, which empty into the thoracic duct and eventually enter the systemic venous circulation at the junction of the left subclavian vein and left internal jugular vein. 

The triacylglycerols are incorporated into a heterogeneous population of spherical lipoprotein particles known as chylomicrons (diameter, 75-600 nm) that contain about 89% triacylglycerol, 8% phospholipid, 2% cholesterol, and 1 % protein. Phospholipids of the chylomicron arise by de novo synthesis (Chapter 19) or from reacylation of absorbed lysolecithin. Cholesterol is supplied by de novo synthesis (Chapter 19) or is absorbed. The protein apolipoprotein B-48 (apo B-48) forms a characteristic protein complement of chylomicrons and is synthesized in the enterocyte. Synthesis of apo B-48 is an obligatory step in chylomicron formation. Absence of apo B-48 synthesis, as in the rare hereditary disease abetalipoproteinemia,... 

Normally more than 95% of ingested lipid is absorbed. When a large fraction is excreted in the feces, it is called steatorrhea. Measurement of fecal lipid with adequate lipid intake is a sensitive indicator of lipid malabsorption. Malabsorption can result from impairment in lipolysis (Table 12-6), micelle formation (Table 12-7), absorption, chylomicron formation, or transport of chylomicrons via the lymph to blood. 

VLDLs are produced by the parenchymal cells of the liver from lipid and apoprotein constituents in a way similar to that of chylomicron formation in enterocytes. However, while the triacylglycerol core of chylomicrons is derived exclusively from absorbed dietary fatty acids and monoa-cylglycerols, VLDL triacylglycerols derive from... 

From the results of animal studies, it is conceivable that DAG may improve postprandial lipemia in humans. Human studies have been conducted to compare the postprandial states of lipids in serum and also in remnant-like particles. Taguchi et al. (7) showed that TG concentrations in chylomicron fraction were markedly lower after ingestion of DAG than after TAG. The lower serum TG levels after DAG ingestion may be the result of the slower rate of chylomicron formation after DAG ingestion compared with TAG ingestion. 

A further understanding of the nature of the chylomicron protein may derive from studies of chylomicron formation in patients with congenital deficiency of the plasma high-density (Fredrickson, 1961) or low-density lipoproteins (Salt et al., 1960a,b) (see Section VI, F for details). 

The presence of LDL in chylomicrons has been detected by immunochemical means (Middleton, 1956 Scanu and Page, 1959). A functional role of this lipoprotein in chylomicron formation has been suggested by the observation that patients with congenital deficiency of LDL, a rare disorder (see Section VI, F, 2, b) do not form chylomicrons. Direct experimental proof is not presently available to support a cause-eflEect relationship between deficiency of LDL and the abnormal absorptive process. 

We had hypothesized that a possible mechanism leading to an attenuated response to an acute fat load of saturated fat might be a temporary retention of triglycerides in the intestinal mucosa during the process of chylomicron formation and release. In order to evaluate that possibility we took small intestinal biopsies via an upper endoscopy 5 h after the beginning of the fat load. 

Karmen, A., M. Whyte, and D. S. Goodman Fatty acid esterification and chylomicron formation during fat absorption. 1. Triglycerides and cholesterol esters. J. Lipid Res. 4, 312—321 (1963). 

Whyte, M., A. Karmen, and D. S. Goodman Fatty acid esterification and chylomicron formation during fat absorption 2. Phospholipids. J. Lipid Res. 4, 322—329 (1963). Williams, J. W., R. L. Baldwin, W. M. Saunders, and P. G. Squire Boundary spreading in sedimentation velocity experiments. The degredation of serum globulin. J. Amer. Chem. Soc. 74, 1542—1548 (1952). 

It has not been established whether the HDL peptide is present or absent in the chylomicrons of patients with TD. If, as seems very likely, the HDL peptide is missing in the chylomicrons of TD, one has to conclude that it is not necessary for chylomicron formation (Fredrickson 1966), in contrast to the j8-lipoprotein peptide, the absence of which (a-jS-lipoproteinemia) results in an inability of chylomicron formation or release. 

Limitation of fat intake represents the most effective tool in exogenous hyperlipemia. The amount of fat tolerated will vary in different individuals, but probably should never exceed 15% of total calories. The kind of fat seems to be of minor importance with regard to control of exogenous hyperlipemia but in view of the fat restriction a sufficient intake of linoleate should be assured. Wilkinson (1956), because of the delayed clearing of alimentary fat, has recommended a program of spaced fat feeding (one fat meal per day). Medium chain triglyceride has been recommended by Ahrens and Spritz (1963) and Furman et al. (1963) because of its absorption into the portal circulation (Bloom et al. 1951) and consequent lack of contribution to chylomicron formation (Job ST and Schett-LER 1956). 

R. M. Glickman and K. Kirsch, Lymph chylomicron formation during... 

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