Triglyceride:rich lipoproteins

Intestinally derived triglyceride-rich lipoprotein. Lipoprotein Metabolism... 

VAN HET HOF K H, DE BOER B C, TIJBURG L B, LUCIUS B R, ZIJP I, WEST C E, HAUTVAST J G and WESTRATE J A (2000) Carotenoid bioavailability in humans from tomatoes processed in different ways determined from the carotenoid response in the triglyceride-rich lipoprotein fraction of plasma after a single consumption and in plasma after 4 days of consumption. JNutr 130(5) 1189-96. 

VAN VLIET T, SCHREURS w H and VAN DEN BERG H (1995) Intestinal beta-carotene absorption and cleavage in men response to beta-carotene and retinyl esters in the triglyceride-rich lipoprotein fi action after a single oral dose of beta-carotene. Am J Clin Nutr 62(1) 110-16. 

This approach can be used only for fat-soluble compounds that follow the same lymphatic route to be transported to the liver as carotenoids. The bioavailability of the compound of interest is determined by monitoring the appearance of the compound and its newly formed intestinal metabolites in the postprandial chylomicron fraction of plasma [also called the density < 1.006 kg/L fraction or triglyceride-rich lipoprotein (TRL) fraction because it is generally a mixture of chylomicrons (CMs) and very low density lipoproteins (VLDLs)] as a function of the time after ingestion. 

Fibrates work by reducing apolipoproteins B, C-III (an inhibitor of LPL), and E, and increasing apolipoproteins A-I and A-II through activation of peroxisome proliferator-activated receptors-alpha (PPAR-a), a nuclear receptor involved in cellular function. The changes in these apolipoproteins result in a reduction in triglyceride-rich lipoproteins (VLDL and IDL) and an increase in HDL. 

Gemfibrozil reduces the synthesis of VLDL and, to a lesser extent, apolipoprotein B with a concurrent increase in the rate of removal of triglyceride-rich lipoproteins from plasma. Clofibrate is less effective than gemfibrozil or niacin in reducing VLDL production. 

Parsy et al. (P6) observed abnormal metabolites of apo-B100-containing lipoproteins, linking these metabolites to accumulation of triglyceride-rich particles containing Lp(a). The excellent correlations found between Lp(a) concentrations and VLDL cholesterol and triglycerides support the hypothesis of a close link between Lp(a) and triglyceride-rich lipoproteins in nephrosis (S42). 

Observations in different types of primary hyperlipidemia revealed in general an inverse correlation between Lp(a) concentrations and plasma triglyceride and triglyceride-rich lipoprotein concentrations in hypertriglyceridemic subjects (A 10, B22, H30, W11). As far as this observation is not troubled by technical problems in the analysis (E8), the possibility exists that Lp(a) catabolism is partly related to the catabolism of triglyceride-rich and/or cholesterol-rich particles (P10, R16). 

Similar problems occur for the nephelometric and turbidimetric methods, where the sizes of the IgG-Lp(a) complexes depend upon that of apo(a) itself (L2, W4). Furthermore, problems due to interferences from elevated plasma triglyceride are commonly encountered in the precipitation techniques (C3). As Lp(a) can be redistributed among the Lp(a) fraction and the triglyceride-rich lipoproteins, especially in patients after a fatty meal (B11), these methods are not appropriate for monitoring Lp(a) levels and distribution in plasma. 

As discussed above, insulin suppresses the breakdown of triglyceride within fat cells in the post-prandial period, preventing release of fatty acids from adipocytes in healthy individuals. Insulin also stimulates triglyceride clearance from triglyceride-rich lipoprotein particles and the esterification of fatty acids to form the intra-adipocyte triglyceride store. 

Pharmacology Fenofibric acid, the active metabolite of fenofibrate, produces reductions in total cholesterol, LDL cholesterol, apo B, total triglycerides, and triglyceride rich lipoprotein (VLDL) in treated patients. In addition, treatment with fenofibrate results in increases in high-density lipoprotein (HDL) and apoproteins apoAl and apoAII. 

Seeballuck, F., Lawless, E., Ashford, M. B., and O Driscoll, C. M. (2004). Stimulation of triglyceride-rich lipoprotein secretion by polysorbate 80 In vitro and in vivo correlation using Caco-2 cells and a cannulated rat intestinal lymphatic model. Pharm. Res. 21, 2320-2326. 

Mechanism of Action An antihyperlipidemic that enhances synthesis of lipoprotein lipase and reduces triglyceride-rich lipoproteins and VLDLs. Therapeutic Effect Increases VLDL catabolism and reduces total plasma triglyceride levels. Pharmacokinetics Well absorbed from the GI tract. Absorption increased when given with food. Protein binding 99%. Rapidly metabolized in the liver to active metabolite. Excreted primarily in urine lesser amount in feces. Not removed by hemodialysis. Half-life 20 hr. 

Mizuguchi, H., Kudo, N., Ohya, T. Kawashima, Y. (1999) Effects of tiadenol and di-(2-ethyl-hexyl)phthalate on the metabolism of phosphatidylcholine and phosphatidylethanolamine in the liver of rats comparison with clofibric acid. Biochem. Pharmacol, 57, 869-876 Mocchiutti, N.O. Bernal, C.A. (1997) Effects of chronic di(2-ethylhexyl) phthalate intake on the secretion and removal rate of triglyceride-rich lipoproteins in rats. Food chem. Toxicol, 35, 1017-1021... 

In the presence of hypertriglyceridemia, HDL cholesterol is low because of exchange of cholesteryl esters from HDL into triglyceride-rich lipoproteins. Treatment of the hypertriglyceridemia may increase or normalize the HDL level. 

Low LPL activity can also be found secondary to metabolic dysregulation, notably in insulin resistance and type 2 diabetes mellitus. In fact, diabetic hypertriglyceridemia is caused in part by decreased LPL secretion in response to reduced insulin action. Another preanalytical pitfall results from the high affinity of LPL for triglyceride-rich lipoproteins. When extremely hypertriglyceridemic plasma is prepared by cen-... 

Field, F., E. Albright, and S. Mathur. 1988. Regulation of triglyceride-rich lipoprotein secretion by fatty acids in Caco-2 cells. J Lipid Res 29 1427. 

J. Heeren and U. Beisiegel, Intracellular metabolism of triglyceride-rich lipoproteins, Curr. Opin. Lipidol. 12 (2001) 255-260. 

TRL, triglyceride-rich lipoproteins that include VLDL and chylomicrons LDL, low-density lipoproteins HDL, high-density lipoproteins LPDP, lipoprotein-deficient plasma. b Significantly different from the corresponding preprandial value (p < 0.05). 

Mocchiutti NO, Bernal CA. 1997. Effects of chronic di(2-ethylhexyl) phthalate intake on the secretion and removal rate of triglyceride-rich lipoproteins in rats. Food Chem Toxicol35 1017-1021. 

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). 

In normolipidemic subjects, apoE is found not only in HDLc-like particles but also in two other fractions associated with triglyceride-rich lipoproteins. These are VLDL, and a lipoprotein class intermediate in size between VLDL and LDL (G3). The latter may be the normal counterpart of the (3-VLDL which accumulates in Type III hyperlipoproteinemia and in cholesterol-fed animals. 

It is likely that the major site of uptake of apoE-containing remnants of the triglyceride-rich lipoproteins is the liver. As apoC is removed and the apoE apoC ratio rises, so the remnant lipoprotein becomes more amenable to hepatic uptake by specific receptors (S25, S28, W16, W17). VLDL remnants and IDL also experience apoE-mediated binding by apoB,E receptors in hepatic cell membrane preparations (H35, Mil). The smallest apoE-rich VLDL subfractions from normolipidemic human plasma compete with LDL for fibroblast (apoB-100,E) receptors in vitro (T10) and in cultured fibroblasts (F17, G2, 17). ... 

---