|
|
||||||||
Journal of Lipid Research, Vol 38, 2173-2192, Copyright © 1997 by Lipid Research, Inc.
REVIEWS |
AD Cooper
Research Institute, Palo Alto Medical Foundation, CA 94301, USA.
Chylomicrons are formed in the intestine and transport dietary triglyceride to peripheral tissues and cholesterol to the liver. The enzyme lipoprotein lipase, with apolipoprotein (apo)C-II as a co- factor, hydrolyzes chylomicron triglyceride allowing the delivery of free fatty acids to muscle and adipose tissue. As a result, a new particle called a chylomicron remnant is formed. This particle is enriched in cholesteryl ester and fat-soluble vitamins and contains apoB-48 and apoE. It is rapidly removed from the circulation by the liver. ApoE is the moiety required for rapid hepatic removal. Its activity is inhibited by C apolipoproteins, especially apoC-I. Hepatic removal appears to be accomplished by several overlapping mechanisms. The particle must first achieve a size that allows it to be "sieved" through the endothelial fenestre allowing entrance into the space of Disse. Here, it may 1) be removed directly by LDL receptors; 2) acquire additional apoE that is secreted free into the space, and then be removed directly by the LDL receptor-related protein (LRP); or 3) it may be sequestered in the space. Sequestration occurs by binding of apoE to heparan sulfate proteoglycans and/or binding of apoB to hepatic lipase. Sequestered particles may be further metabolized allowing apoE, and lysophospholipid enrichment, followed by transfer to one of the above receptors for hepatic uptake. The above formulation is based upon animal studies. In humans, delayed removal of chylomicron remnants has been documented in diabetes, renal failure, and familial combined hyperlipemia and is the abnormality resulting in type III hyperlipidemia. Case control studies have identified delayed remnant removal as an independent risk factor for atherosclerotic cardiovascular disease. Thus, understanding the further details of the processes, and how it can be regulated in humans, is an important challenge for the future.
This article has been cited by other articles:
![]() |
A. P. Lillis, L. B. Van Duyn, J. E. Murphy-Ullrich, and D. K. Strickland LDL Receptor-Related Protein 1: Unique Tissue-Specific Functions Revealed by Selective Gene Knockout Studies Physiol Rev, July 1, 2008; 88(3): 887 - 918. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Altenburg, J. Arbones-Mainar, L. Johnson, J. Wilder, and N. Maeda Human LDL Receptor Enhances Sequestration of ApoE4 and VLDL Remnants on the Surface of Hepatocytes but Not Their Internalization in Mice Arterioscler. Thromb. Vasc. Biol., June 1, 2008; 28(6): 1104 - 1110. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. J. Goldberg, Y. Hu, H.-L. Noh, J. Wei, L. A. Huggins, M. G. Rackmill, H. Hamai, B. N. Reid, W. S. Blaner, and L.-S. Huang Decreased Lipoprotein Clearance Is Responsible for Increased Cholesterol in LDL Receptor Knockout Mice With Streptozotocin-Induced Diabetes Diabetes, June 1, 2008; 57(6): 1674 - 1682. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Charlton-Menys and P. N. Durrington Human cholesterol metabolism and therapeutic molecules Exp Physiol, January 1, 2008; 93(1): 27 - 42. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Guerin, W. Le Goff, E. Duchene, Z. Julia, T. Nguyen, T. Thuren, C. L. Shear, and M. J. Chapman Inhibition of CETP by Torcetrapib Attenuates the Atherogenicity of Postprandial TG-Rich Lipoproteins in Type IIB Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., January 1, 2008; 28(1): 148 - 154. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Pocathikorn, R. R. Taylor, I. James, and C. D. S. Mamotte LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism J. Nutr., September 1, 2007; 137(9): 2062 - 2067. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. H. Nelson, D. S. Edgerton, R. Basu, J. C. Roesner, A. D. Cherrington, and J. M. Miles Triglyceride Uptake and Lipoprotein Lipase-Generated Fatty Acid Spillover in the Splanchnic Bed of Dogs Diabetes, July 1, 2007; 56(7): 1850 - 1855. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Gao, H. Katagiri, Y. Ishigaki, T. Yamada, T. Ogihara, J. Imai, K. Uno, Y. Hasegawa, M. Kanzaki, T. T. Yamamoto, et al. Involvement of Apolipoprotein E in Excess Fat Accumulation and Insulin Resistance Diabetes, January 1, 2007; 56(1): 24 - 33. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. B. Cesar, M. R. M. Oliveira, C. H. Mesquita, and R. C. Maranhao High Cholesterol Intake Modifies Chylomicron Metabolism in Normolipidemic Young Men J. Nutr., April 1, 2006; 136(4): 971 - 976. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. E. Kypreos and V. I. Zannis LDL receptor deficiency or apoE mutations prevent remnant clearance and induce hypertriglyceridemia in mice J. Lipid Res., March 1, 2006; 47(3): 521 - 529. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. N. Ginsberg REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 383 - 392. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Asahina, M. Sato, and K. Imaizumi Genetic analysis of diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats J. Lipid Res., October 1, 2005; 46(10): 2289 - 2294. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Carpenter, Y. Lin, S. Stoll, R. L. Raffai, R. McCuskey, and R. Wang VEGF is crucial for the hepatic vascular development required for lipoprotein uptake Development, July 15, 2005; 132(14): 3293 - 3303. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Linke, H. Dawson, and E. H. Harrison Isolation and Characterization of a Microsomal Acid Retinyl Ester Hydrolase J. Biol. Chem., June 17, 2005; 280(24): 23287 - 23294. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Zhang, R. Lopez-Ridaura, E. B Rimm, N. Rifai, D. J Hunter, and F. B Hu Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1429 - 1435. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Out, M. Hoekstra, S. C. A. de Jager, P. de Vos, D. R. van der Westhuyzen, N. R. Webb, M. Van Eck, E. A. L. Biessen, and T. J. C. Van Berkel Adenovirus-mediated hepatic overexpression of scavenger receptor class B type I accelerates chylomicron metabolism in C57BL/6J mice J. Lipid Res., June 1, 2005; 46(6): 1172 - 1181. [Abstract] [Full Text] [PDF] |
||||
![]() |
G D Kolovou, K K Anagnostopoulou, and D V Cokkinos Pathophysiology of dyslipidaemia in the metabolic syndrome Postgrad. Med. J., June 1, 2005; 81(956): 358 - 366. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Hamsten, A. Silveira, S. Boquist, R. Tang, M. G. Bond, U. de Faire, and J. Bjorkegren The apolipoprotein CI content of triglyceride-rich lipoproteins independently predicts early atherosclerosis in healthy middle-aged men J. Am. Coll. Cardiol., April 5, 2005; 45(7): 1013 - 1017. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Chan, G. F. Watts, T. W.K. Ng, Y. Uchida, N. Sakai, S. Yamashita, and P. H. R. Barrett Adiponectin and other Adipocytokines as Predictors of Markers of Triglyceride-Rich Lipoprotein Metabolism Clin. Chem., March 1, 2005; 51(3): 578 - 585. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Futamura, P. Dhanasekaran, T. Handa, M. C. Phillips, S. Lund-Katz, and H. Saito Two-step Mechanism of Binding of Apolipoprotein E to Heparin: IMPLICATIONS FOR THE KINETICS OF APOLIPOPROTEIN E-HEPARAN SULFATE PROTEOGLYCAN COMPLEX FORMATION ON CELL SURFACES J. Biol. Chem., February 18, 2005; 280(7): 5414 - 5422. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-H. Chung, B. S. Cho, P. Liang, S. Doran, L. Osterlund, R. A Oster, B. Darnell, and F. Franklin Contribution of postprandial lipemia to the dietary fat-mediated changes in endogenous lipoprotein-cholesterol concentrations in humans Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1145 - 1158. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Wassef, L. Bernier, J. Davignon, and J. S. Cohn Synthesis and Secretion of ApoC-I and ApoE during Maturation of Human SW872 Liposarcoma Cells J. Nutr., November 1, 2004; 134(11): 2935 - 2941. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. L. Dichek, K. Qian, and N. Agrawal Divergent Effects of the Catalytic and Bridging Functions of Hepatic Lipase on Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2004; 24(9): 1696 - 1702. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-H. Chung, P. Liang, S. Doran, B. H. S. Cho, and F. Franklin Postprandial chylomicrons: potent vehicles for transporting cholesterol from endogenous LDL+HDL and cell membranes to the liver via LCAT and CETP J. Lipid Res., July 1, 2004; 45(7): 1242 - 1255. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Quadro, L. Hamberger, M. E. Gottesman, V. Colantuoni, R. Ramakrishnan, and W. S. Blaner Transplacental delivery of retinoid: the role of retinol-binding protein and lipoprotein retinyl ester Am J Physiol Endocrinol Metab, June 1, 2004; 286(5): E844 - E851. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Out, J. K. Kruijt, P. C. N. Rensen, R. B. Hildebrand, P. de Vos, M. Van Eck, and T. J. C. Van Berkel Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism J. Biol. Chem., April 30, 2004; 279(18): 18401 - 18406. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. L. Dichek, K. Qian, and N. Agrawal The bridging function of hepatic lipase clears plasma cholesterol in LDL receptor-deficient "apoB-48-only" and "apoB-100-only" mice J. Lipid Res., March 1, 2004; 45(3): 551 - 560. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. I. Malloy, M. K. Altenburg, C. Knouff, L. Lanningham-Foster, J. S. Parks, and N. Maeda Harmful Effects of Increased LDLR Expression in Mice With Human APOE*4 But Not APOE*3 Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 91 - 97. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Fu, K. F. Kozarsky, and J. Borensztajn Overexpression of SR-BI by Adenoviral Vector Reverses the Fibrateinduced Hypercholesterolemia of Apolipoprotein E-deficient Mice J. Biol. Chem., December 26, 2003; 278(52): 52559 - 52563. [Abstract] [Full Text] [PDF] |
||||
![]() |
E S. Tai, D. Corella, M. Deurenberg-Yap, J. Cutter, S. K. Chew, C. E. Tan, and J. M. Ordovas Dietary Fat Interacts with the -514C>T Polymorphism in the Hepatic Lipase Gene Promoter on Plasma Lipid Profiles in a Multiethnic Asian Population: The 1998 Singapore National Health Survey J. Nutr., November 1, 2003; 133(11): 3399 - 3408. [Abstract] [Full Text] [PDF] |
||||
![]() |
B.-H. Chung, S. Doran, P. Liang, L. Osterlund, B. S. Cho, R. A Oster, B. Darnell, and F. Franklin Alcohol-mediated enhancement of postprandial lipemia: a contributing factor to an increase in plasma HDL and a decrease in risk of cardiovascular disease Am. J. Clinical Nutrition, September 1, 2003; 78(3): 391 - 399. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. G. Parhofer, E. Laubach, and P. H. R. Barrett Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients J. Lipid Res., June 1, 2003; 44(6): 1192 - 1198. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Saito, P. Dhanasekaran, D. Nguyen, F. Baldwin, K. H. Weisgraber, S. Wehrli, M. C. Phillips, and S. Lund-Katz Characterization of the Heparin Binding Sites in Human Apolipoprotein E J. Biol. Chem., April 18, 2003; 278(17): 14782 - 14787. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Hidaka, M. Tozuka, B. Meyer, K. Yamauchi, M. Sugano, T. Nakabayashi, and T. Katsuyama Characterization of Triglyceride Rich Lipoproteins with Very Light Density by Ultracentrifugation and Agarose Gel Electrophoresis using Triglyceride- and Cholesterol-Staining Ann. Clin. Lab. Sci., April 1, 2003; 33(2): 167 - 178. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Rudenko, L. Henry, K. Henderson, K. Ichtchenko, M. S. Brown, J. L. Goldstein, and J. Deisenhofer Structure of the LDL Receptor Extracellular Domain at Endosomal pH Science, December 20, 2002; 298(5602): 2353 - 2358. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. N. Ginsberg New Perspectives on Atherogenesis: Role of Abnormal Triglyceride-Rich Lipoprotein Metabolism Circulation, October 15, 2002; 106(16): 2137 - 2142. [Full Text] [PDF] |
||||
![]() |
Y. Kako, M. Masse, L.-S. Huang, A. R. Tall, and I. J. Goldberg Lipoprotein lipase deficiency and CETP in streptozotocin-treated apoB-expressing mice J. Lipid Res., June 1, 2002; 43(6): 872 - 877. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Chan, G. F. Watts, P. H. R. Barrett, I. J. Martins, A. P. James, J. C. L. Mamo, T. A. Mori, and T. G. Redgrave Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test J. Lipid Res., May 1, 2002; 43(5): 706 - 712. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. Chen, R. L Fitzgerald, and G. Schonfeld Hypobetalipoproteinemic Mice with a Targeted Apolipoprotein (Apo) B-27.6-specifying Mutation. IN VIVO EVIDENCE FOR AN IMPORTANT ROLE OF AMINO ACIDS 1254-1744 OF ApoB IN LIPID TRANSPORT AND METABOLISM OF THE ApoB-CONTAINING LIPOPROTEIN J. Biol. Chem., April 12, 2002; 277(16): 14135 - 14145. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. L. Raffai and K. H. Weisgraber Hypomorphic Apolipoprotein E Mice. A NEW MODEL OF CONDITIONAL GENE REPAIR TO EXAMINE APOLIPOPROTEIN E-MEDIATED METABOLISM J. Biol. Chem., March 22, 2002; 277(13): 11064 - 11068. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. C. Chan, G. F. Watts, P. H. Barrett, J. C.L. Mamo, and T. G. Redgrave Markers of Triglyceride-rich Lipoprotein Remnant Metabolism in Visceral Obesity Clin. Chem., February 1, 2002; 48(2): 278 - 283. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Schreyer, C. Vick, T. C. Lystig, P. Mystkowski, and R. C. LeBoeuf LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E207 - E214. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Hidaka, M. Tozuka, E. Hidaka, K. Yamauchi, H. Ota, T. Honda, and T. Katsuyama Characterization of an Apolipoprotein E3 Variant (Arg 145 -> His) Associated with Mild Hypertriglyceridemia Ann. Clin. Lab. Sci., April 1, 2001; 31(2): 163 - 170. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. Bravo, A. Cantafora, M. Avella, and K. M. Botham Metabolism of Chylomicron Cholesterol Is Delayed by Estrogen. An In Vivo Study in the Rat Experimental Biology and Medicine, February 1, 2001; 226(2): 112 - 118. [Abstract] [Full Text] |
||||
![]() |
R. Abia, Y. M. Pacheco, J. S. Perona, E. Montero, F. J. G. Muriana, and V. Ruiz-Gutiérrez The Metabolic Availability of Dietary Triacylglycerols from Two High Oleic Oils during the Postprandial Period Does Not Depend on the Amount of Oleic Acid Ingested by Healthy Men J. Nutr., January 1, 2001; 131(1): 59 - 65. [Abstract] [Full Text] |
||||
![]() |
K. C-W. Yu, Y. Jiang, W. Chen, and A. D. Cooper Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E J. Lipid Res., November 1, 2000; 41(11): 1715 - 1727. [Abstract] [Full Text] |
||||
![]() |
J. Dong, M. E. Balestra, Y. M. Newhouse, and K. H. Weisgraber Human apolipoprotein E7: lysine mutations in the carboxy-terminal domain are directly responsible for preferential binding to very low density lipoproteins J. Lipid Res., November 1, 2000; 41(11): 1783 - 1789. [Abstract] [Full Text] |
||||
![]() |
J. D. Medh, G. L. Fry, S. L. Bowen, S. Ruben, H. Wong, and D. A. Chappell Lipoprotein lipase- and hepatic triglyceride lipase- promoted very low density lipoprotein degradation proceeds via an apolipoprotein E-dependent mechanism J. Lipid Res., November 1, 2000; 41(11): 1858 - 1871. [Abstract] [Full Text] |
||||
![]() |
J. P. Weichert, F. T. Lee Jr, S. G. Chosy, M. A. Longino, J. E. Kuhlman, D. M. Heisey, and G. E. Leverson Combined Hepatocyte-selective and Blood-Pool Contrast Agents for the CT Detection of Experimental Liver Tumors in Rabbits Radiology, September 1, 2000; 216(3): 865 - 871. [Abstract] [Full Text] |
||||
![]() |
A. M. Minihane, S. Khan, E. C. Leigh-Firbank, P. Talmud, J. W. Wright, M. C. Murphy, B. A. Griffin, and C. M. Williams ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype Arterioscler. Thromb. Vasc. Biol., August 1, 2000; 20(8): 1990 - 1997. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. H. Chung and N. Dashti Lipolytic remnants of human VLDL produced in vitro: effect of HDL levels in the lipolysis mixtures on the apoCs to apoE ratio and metabolic properties of VLDL core remnants J. Lipid Res., February 1, 2000; 41(2): 285 - 297. [Abstract] [Full Text] |
||||
![]() |
R. Abia, J. S. Perona, Y. M. Pacheco, E. Montero, F. J. G. Muriana, and V. Ruiz-Gutiérrez Postprandial Triacylglycerols from Dietary Virgin Olive Oil Are Selectively Cleared in Humans J. Nutr., December 1, 1999; 129(12): 2184 - 2191. [Abstract] [Full Text] |
||||
![]() |
R. W. Mahley, Y. Huang, and S. C. Rall , Jr. Pathogenesis of type III hyperlipoproteinemia (dysbetalipoproteinemia): questions, quandaries, and paradoxes J. Lipid Res., November 1, 1999; 40(11): 1933 - 1949. [Abstract] [Full Text] |
||||
![]() |
S. Swarnakar, R. E. Temel, M. A. Connelly, S. Azhar, and D. L. Williams Scavenger Receptor Class B, Type I, Mediates Selective Uptake of Low Density Lipoprotein Cholesteryl Ester J. Biol. Chem., October 15, 1999; 274(42): 29733 - 29739. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. C-W. Yu, Y. Jiang, W. Chen, and A. D. Cooper Evaluation of the components of the chylomicron remnant removal mechanism by use of the isolated perfused mouse liver J. Lipid Res., October 1, 1999; 40(10): 1899 - 1910. [Abstract] [Full Text] |
||||
![]() |
N. Mero, L. Suurinkeroinen, M. Syvänne, P. Knudsen, H. Yki-Järvinen, and M.-R. Taskinen Delayed clearance of postprandial large TG-rich particles in normolipidemic carriers of LPL Asn291Ser gene variant J. Lipid Res., September 1, 1999; 40(9): 1663 - 1670. [Abstract] [Full Text] |
||||
![]() |
C. T Phan, B.-C. Mortimer, I. J Martins, and T. G Redgrave Plasma clearance of chylomicrons from butterfat is not dependent on saturation: studies with butterfat fractions and other fats containing triacylglycerols with low or high melting points Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1151 - 1161. [Abstract] [Full Text] [PDF] |
||||
![]() |
F. T. Yen, M. Masson, N. Clossais-Besnard, P. Andre, J.-M. Grosset, L. Bougueleret, J.-B. Dumas, O. Guerassimenko, and B. E. Bihain Molecular Cloning of a Lipolysis-stimulated Remnant Receptor Expressed in the Liver J. Biol. Chem., May 7, 1999; 274(19): 13390 - 13398. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. E. Crawford and J. Borensztajn Plasma clearance and liver uptake of chylomicron remnants generated by hepatic lipase lipolysis: evidence for a lactoferrin-sensitive and apolipoprotein E-independent pathway J. Lipid Res., May 1, 1999; |