Abstract
Cardiovascular disease can be considered a condition of chronic low-grade inflammation. Postprandial hyperlipidemia and obesity can both exacerbate inflammatory processes. Postprandial lipemia stimulates the activation of leukocytes, the production of chemokines, and activation of the complement system. Obesity is also associated with postprandial hyperlipidemia by hepatic overproduction of very low-density lipoprotein (VLDL) and consequently delayed clearance of intestinally derived chylomicrons due to competition for the same metabolic pathways. Insulin resistance is one of the key elements leading to hepatic VLDL overproduction and is also a key factor in the generation of inflammation. These metabolic derangements cause accumulation of atherogenic remnant lipoproteins, which is also a proatherogenic mechanism. Change in lifestyle is the most important therapeutic strategy to stop this vicious circle of postprandial hyperlipidemia, obesity, inflammation, insulin resistance, and cardiovascular disease.
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Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431–8.
Zilversmit DB. Atherogenesis: a postprandial phenomenon. Circulation. 1979;60:473–85.
Cohn JS. Postprandial lipemia and remnant lipoproteins. Clin Lab Med. 2006;26:773–86.
Alipour A, van Oostrom AJ, Izraeljan A, et al. Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol. 2008;28:792–7.
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298:299–308.
van Oostrom AJ, van Wijk JP, Sijmonsma TP, Rabelink TJ, Castro Cabezas M. Increased expression of activation markers on monocytes and neutrophils in type 2 diabetes. Neth J Med. 2004;62:320–5.
Cohn JS, Johnson EJ, Millar JS, et al. Contribution of apoB-48 and apoB-100 triglyceride-rich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters. J Lipid Res. 1993;34:2033–40.
Irving BA, Nair KS, Srinivasan M. Effects of insulin sensitivity, body composition, and fitness on lipoprotein particle sizes and concentrations determined by nuclear magnetic resonance. J Clin Endocrinol Metab. 2011;96:E713–8.
Dole VP, Hamlin 3rd JT. Particulate fat in lymph and blood. Physiol Rev. 1962;42:674–701.
Haberbosch W, Poli A, Augustin J. Characterization of human chylomicrons. Biochim Biophys Acta. 1982;713:398–409.
Hussain MM, Kedees MH, Singh K, Athar H, Jamali NZ. Signposts in the assembly of chylomicrons. Front Biosci. 2001;6:D320–31.
• Iqbal J, Hussain MM: Intestinal lipid absorption. Am J Physiol Endocrinol Metab 2009, 296:E1183–1194. This is an excellent review on the intracellular processes involved in intestinal lipid absorption and chylomicron formation.
Phillips C, Mullan K, Owens D, Tomkin GH. Intestinal microsomal triglyceride transfer protein in type 2 diabetic and non-diabetic subjects: the relationship to triglyceride-rich postprandial lipoprotein composition. Atherosclerosis. 2006;187:57–64.
• Siddiqi S, Saleem U, Abumrad NA, et al.: A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER. J Lipid Res 2010, 51:1918–28. This study identified multiple proteins responsible for the formation of prechylomicron transport vesicles.
Mansbach 2nd CM, Gorelick F. Development and physiological regulation of intestinal lipid absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons. Am J Physiol Gastrointest Liver Physiol. 2007;293:G645–50.
Mansbach CM, Siddiqi SA. The biogenesis of chylomicrons. Annu Rev Physiol. 2010;72:315–33.
Schaefer EJ, Wetzel MG, Bengtsson G, et al. Transfer of human lymph chylomicron constituents to other lipoprotein density fractions during in vitro lipolysis. J Lipid Res. 1982;23:1259–73.
Ehnholm C, Mahley RW, Chappell DA, et al. Role of apolipoprotein E in the lipolytic conversion of beta-very low density lipoproteins to low density lipoproteins in type III hyperlipoproteinemia. Proc Natl Acad Sci U S A. 1984;81:5566–70.
•• Beigneux AP, Franssen R, Bensadoun A, et al.: Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase. Arterioscler Thromb Vasc Biol. 2009, 29:956–62. This interesting study identified a mutation in GPIHBP1 in a patient with chylomicronemia and confirmed that GPIHBP1 is necessary for binding LPL with chylomicrons in a mouse model.
•• Weinstein MM, Yin L, Tu Y, et al.: Chylomicronemia elicits atherosclerosis in mice--brief report. Arterioscler Thromb Vasc Biol 2010, 30:20–3. This study shows a direct relationship between chylomicronemia and atherosclerosis in mice and describes an interesting mouse model to further investigate this relationship.
Goldberg IJ, Eckel RH, Abumrad NA. Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways. J Lipid Res. 2009;50(Suppl):S86–90.
Bharadwaj KG, Hiyama Y, Hu Y, et al. Chylomicron- and VLDL-derived lipids enter the heart through different pathways: in vivo evidence for receptor- and non-receptor-mediated fatty acid uptake. J Biol Chem. 2010;285:37976–86.
De Bruin TW, Brouwer CB, Gimpel JA, Erkelens DW. Postprandial decrease in HDL cholesterol and HDL apo A-I in normal subjects in relation to triglyceride metabolism. Am J Physiol. 1991;260:E492–8.
Erkelens DW, de Bruin TW, Castro Cabezas M. Tulp syndrome. Lancet. 1993;342:1536–7.
Barritt DW. Alimentary lipaemia in men with coronary artery disease and in controls. Br Med J. 1956;2:640–4.
Brown DF, Kinch SH, Doyle JT. Serum triglycerides in health and in ischemic heart disease. N Engl J Med. 1965;273:947–52.
de Groot LC, van Staveren WA, Burema J. Survival beyond age 70 in relation to diet. Nutr Rev. 1996;54:211–2.
Weintraub MS, Grosskopf I, Rassin T, et al. Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years. BMJ. 1996;312:935–9.
Patsch JR, Miesenbock G, Hopferwieser T, et al. Relation of triglyceride metabolism and coronary artery disease. Studies in the postprandial state. Arterioscler Thromb. 1992;12:1336–45.
Karpe F, Steiner G, Uffelman K, Olivecrona T, Hamsten A. Postprandial lipoproteins and progression of coronary atherosclerosis. Atherosclerosis. 1994;106:83–97.
Daskalova DC, Kolovou GD, Panagiotakos DB, Pilatis ND, Cokkinos DV. Increase in aortic pulse wave velocity is associated with abnormal postprandial triglyceride response. Clin Cardiol. 2005;28:577–83.
Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79:350–4.
van Oostrom AJ, Sijmonsma TP, Verseyden C, et al. Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res. 2003;44:576–83.
Castro Cabezas M, Halkes CJ, Meijssen S, van Oostrom AJ, Erkelens DW. Diurnal triglyceride profiles: a novel approach to study triglyceride changes. Atherosclerosis. 2001;155:219–28.
Halkes CJ, Castro Cabezas M, van Wijk JP, Erkelens DW. Gender differences in diurnal triglyceridemia in lean and overweight subjects. Int J Obes Relat Metab Disord. 2001;25:1767–74.
van Oostrom AJ, Castro Cabezas M, Ribalta J, et al. Diurnal triglyceride profiles in healthy normolipidemic male subjects are associated to insulin sensitivity, body composition and diet. Eur J Clin Invest. 2000;30:964–71.
van Wijk JP, Castro Cabezas M, Halkes CJ, Erkelens DW. Effects of different nutrient intakes on daytime triacylglycerolemia in healthy, normolipemic, free-living men. Am J Clin Nutr. 2001;74:171–8.
Geluk CA, Halkes CJ, De Jaegere PP, Plokker TW, Castro Cabezas M. Daytime triglyceridemia in normocholesterolemic patients with premature atherosclerosis and in their first-degree relatives. Metabolism. 2004;53:49–53.
Bansal S, Buring JE, Rifai N, et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298:309–16.
Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302:1993–2000.
Miller M, Stone NJ, Ballantyne C, et al.: Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association Circulation 2011, 123:00–00.
Zilversmit DB. Atherogenic nature of triglycerides, postprandial lipidemia, and triglyceride-rich remnant lipoproteins. Clin Chem. 1995;41:153–8.
Stender S, Zilversmit DB. Comparison of cholesteryl ester transfer from chylomicrons and other plasma lipoproteins to aortic intima media of cholesterol-fed rabbits. Arteriosclerosis. 1982;2:493–9.
Proctor SD, Mamo JC. Intimal retention of cholesterol derived from apolipoprotein B100- and apolipoprotein B48-containing lipoproteins in carotid arteries of Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol. 2003;23:1595–600.
van Oostrom AJ, Rabelink TJ, Verseyden C, et al. Activation of leukocytes by postprandial lipemia in healthy volunteers. Atherosclerosis. 2004;177:175–82.
•• Gower RM, Wu H, Foster GA, et al.: CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. Arterioscler Thromb Vasc Biol 2011, 31:160–166. This excellent study shows a direct relationship between postprandial leukocyte activation with increased vascular adhesion of monocytes postprandially.
Tertov VV, Kalenich OS, Orekhov AN. Lipid-laden white blood cells in the circulation of patients with coronary heart disease. Exp Mol Pathol. 1992;57:22–8.
Bentley C, Hathaway N, Widdows J, et al.: Influence of chylomicron remnants on human monocyte activation in vitro. Nutr Metab Cardiovasc Dis 2010, epublication.
Skrede B, Blomhoff R, Maelandsmo GM, et al. Uptake of chylomicron remnant retinyl esters in human leukocytes in vivo. Eur J Clin Invest. 1992;22:229–34.
Alipour A, Elte JW, van Zaanen HC, Rietveld AP, Castro Cabezas M. Novel aspects of postprandial lipemia in relation to atherosclerosis. Atheroscler Suppl. 2008;9:39–44.
De Pascale C, Avella M, Perona JS, et al. Fatty acid composition of chylomicron remnant-like particles influences their uptake and induction of lipid accumulation in macrophages. Febs J. 2006;273:5632–40.
Botham KM, Moore EH, De Pascale C, Bejta F. The induction of macrophage foam cell formation by chylomicron remnants. Biochem Soc Trans. 2007;35:454–8.
Halkes CJ, van Dijk H, de Jaegere PPT, et al. Postprandial increase of complement component 3 in normolipidemic patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001;21:1526–30.
Scantlebury T, Maslowska M, Cianflone K. Chylomicron-specific enhancement of acylation stimulating protein and precursor protein C3 production in differentiated human adipocytes. J Biol Chem. 1998;273:20903–9.
Alipour A, van Oostrom AJ, Van Wijk JP, et al. Mannose binding lectin deficiency and triglyceride-rich lipoprotein metabolism in normolipidemic subjects. Atherosclerosis. 2009;206:444–50.
Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath Jr CW. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341:1097–105.
Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67:968–77.
Castro Cabezas M, de Bruin TW, de Valk HW, et al. Impaired fatty acid metabolism in familial combined hyperlipidemia. A mechanism associating hepatic apolipoprotein B overproduction and insulin resistance. J Clin Invest. 1993;92:160–8.
Karpe F, Bickerton AS, Hodson L, et al. Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation. Biochem Soc Trans. 2007;35:472–6.
Halkes CJ, Van Wijk JP, Ribalta J, Masana L, Castro Cabezas M. Diurnal triglyceridaemia and insulin resistance in mildly obese subjects with normal fasting plasma lipids. J Intern Med. 2004;255:74–81.
Hsieh J, Hayashi AA, Webb J, Adeli K. Postprandial dyslipidemia in insulin resistance: mechanisms and role of intestinal insulin sensitivity. Atheroscler Suppl. 2008;9:7–13.
Otokozawa S, Ai M, Diffenderfer MR, et al. Fasting and postprandial apolipoprotein B-48 levels in healthy, obese, and hyperlipidemic subjects. Metabolism. 2009;58:1536–42.
Kumar V, Madhu SV, Singh G, Gambhir JK. Post-prandial hypertriglyceridemia in patients with type 2 diabetes mellitus with and without macrovascular disease. J Assoc Physicians India. 2010;58:603–7.
van Wijk JP, de Koning EJ, Castro Cabezas M, Rabelink TJ. Rosiglitazone improves postprandial triglyceride and free fatty acid metabolism in type 2 diabetes. Diabetes Care. 2005;28:844–9.
• van Wijk JP, Hoepelman AI, de Koning EJ, et al.: Differential effects of rosiglitazone and metformin on postprandial lipemia in patients with HIV-lipodystrophy. Arterioscler Thromb Vasc Biol 2011, 31:228–33. An interesting observation showing that rosiglitazone increases postprandial remnant-like particle cholesterol in patients with HIV lipodystrophy, but this was unaffected by metformin.
Duez H, Lamarche B, Valero R, et al. Both intestinal and hepatic lipoprotein production are stimulated by an acute elevation of plasma free fatty acids in humans. Circulation. 2008;117:2369–76.
• McQuaid SE, Hodson L, Neville MJ, et al.: Downregulation of adipose tissue fatty acid trafficking in obesity: a driver for ectopic fat deposition? Diabetes 2011, 60:47–55. This extensive study shows that adipose fat tissue storage after meals is substantially suppressed in obese men, which impairs dietary fat storage.
Wang YI, Schulze J, Raymond N, et al. Endothelial inflammation correlates with subject triglycerides and waist size after a high-fat meal. Am J Physiol Heart Circ Physiol. 2011;300:H784–91.
Mraz M, Lacinova Z, Drapalova J, et al. The effect of very-low-calorie diet on mRNA expression of inflammation-related genes in subcutaneous adipose tissue and peripheral monocytes of obese patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2011;96:E606–13.
Lopez-Miranda J, Williams C, Lairon D. Dietary, physiological, genetic and pathological influences on postprandial lipid metabolism. Br J Nutr. 2007;98:458–73.
Lozano A, Perez-Martinez P, Delgado-Lista J, et al.: Body mass interacts with fat quality to determine the postprandial lipoprotein response in healthy young adults. Nutr Metab Cardiovasc Dis 2010, epublication.
Maraki MI, Aggelopoulou N, Christodoulou N, et al. Lifestyle intervention leading to moderate weight loss normalizes postprandial triacylglycerolemia despite persisting obesity. Obesity (Silver Spring). 2011;19:968–76.
Mestek ML. Physical activity, blood lipids, and lipoproteins. Am J Lifestyle Med. 2009;3:279–83.
van Oostrom AJ, Plokker HW, van Asbeck BS, et al. Effects of rosuvastatin on postprandial leukocytes in mildly hyperlipidemic patients with premature coronary sclerosis. Atherosclerosis. 2006;185:331–9.
Ford ES, Li C, Zhao G, Pearson WS, Mokdad AH. Hypertriglyceridemia and its pharmacologic treatment among US adults. Arch Intern Med. 2009;169:572–8.
• Jun M, Foote C, Lv J, et al.: Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010, 375:1875–1884. This large meta-analysis on fibrates in a heterogeneous population showed a modest reduction in cardiovascular events.
• Aron-Wisnewsky J, Julia Z, Poitou C, et al.: Effect of bariatric surgery-induced weight loss on SR-BI-, ABCG1-, and ABCA1-mediated cellular cholesterol efflux in obese women. J Clin Endocrinol Metab 2011, 96:1151–9. This article shows the positive effects of bariatric surgery in women on lipid metabolism by an increased reverse cholesterol pathway and reduction in cholesteryl ester transfer protein.
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Klop, B., Castro Cabezas, M. Chylomicrons: A Key Biomarker and Risk Factor for Cardiovascular Disease and for the Understanding of Obesity. Curr Cardiovasc Risk Rep 6, 27–34 (2012). https://doi.org/10.1007/s12170-011-0215-z
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DOI: https://doi.org/10.1007/s12170-011-0215-z