Advertisement

Atherogenic Lipid Metabolism in Obesity

  • Sue-Anne Toh
  • Michael Levin
  • Daniel J. Rader
Chapter

Abstract

Atherogenic dyslipidemia, characterized by increased triglyceride-rich lipoproteins (TRLs), increased small dense low density lipoprotein (LDL), and low levels of high density lipoprotein (HDL), is common in obesity. This constellation is often accompanied by insulin resistance and associated with substantially increased risk for cardiovascular disease in these individuals. This chapter details the known molecular mechanisms of adipose tissue and hepatic function, as it pertains to apoB-containing lipoprotein assembly and metabolism, both in the healthy as well as in the obese, insulin resistant state. The mechanisms connecting obesity, insulin resistance, and dyslipidemia are incompletely understood, but are thought to be driven by (a) increased flux of free fatty acids (FFAs) from adipose tissue to liver driving hepatic overproduction of very low density lipoprotein (VLDL), (b) impaired catabolism of atherogenic lipoprotein remnants, and (c) hypercatabolism of HDL. The pathophysiology of each of these, and the implications for cardiovascular disease risk and therapeutics are discussed. The present paradigm is likely oversimplified, and a more thorough understanding of the physiological and molecular mechanisms is critical for improving our approach to managing the influence of obesity on lipoprotein metabolism, and to the development of appropriate therapeutic approaches.

Keywords

Endoplasmic Reticulum Stress Cholesteryl Ester Transfer Protein Hepatic Lipase Microsomal Triglyceride Transfer Protein Atherogenic Dyslipidemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection. (2001). Evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA: The Journal of the American Medical Association, 285(19), 2486–2497.Google Scholar
  2. 2.
    Bays, H. E., González-Campoy, J. M., Bray, G. A., Kitabchi, A. E., Bergman, D. A., Schorr, A. B., et al. (2008). Pathogenic potential of adipose tissue and metabolic consequences of adipocyte hypertrophy and increased visceral adiposity. Expert Review of Cardiovascular Therapy, 6(3), 343–368.CrossRefPubMedGoogle Scholar
  3. 3.
    Sparks, J. D., Collins, H. L., Sabio, I., et al. 1997). Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat hepatoma cells. Biochimica et Biophysica Acta, 1347(1), 51–56.PubMedGoogle Scholar
  4. 4.
    White, A. L., Graham, D. L., LeGros, J., et al. (1992). Oleate-mediated stimulation of apolipoprotein B secretion from rat hepatoma cells: A function of the ability of apolipoprotein B to direct lipoprotein assembly and escape presecretory degradation. The Journal of Biological Chemistry, 267, 15657–15664.PubMedGoogle Scholar
  5. 5.
    Wu, X., Sakata, N., Dixon, J., & Ginsberg, H. N. (1994). Exogenous VLDL stimulates apolipoprotein B secretion from HepG2 cells by both pre- and post-translational mechanisms. Journal of Lipid Research, 35, 1200–1211.PubMedGoogle Scholar
  6. 6.
    Targher, G., Marra, F., & Marchesini, G. (2008). Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: Causal effect or epiphenomenon? Diabetologia, 51(11), 1947–1953. Epub 2008 Sep 2.CrossRefPubMedGoogle Scholar
  7. 7.
    Lewis, G. F., Uffelman, K. D., Szeto, L. W., Weller, B., & Steiner, G. (1995). Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. The Journal of Clinical Investigation, 95(1), 158–166.CrossRefPubMedGoogle Scholar
  8. 8.
    Kissebah, A. H., Alfarsi, S., Evans, D. J. & Adams, P. W. (1982). Integrated regulation of very -low density lipoprotein triglyceride and apolipoprotein-B kinetics in non-insulin dependent diabetes mellitus. Diabetes, 31(3), 217–225.CrossRefPubMedGoogle Scholar
  9. 9.
    Campbell, P. J., Carlson, M. G., & Nurjhan, N. (1994). Fat metabolism in human obesity. The American Journal of Physiology, 266(4 Pt 1), E600–605.PubMedGoogle Scholar
  10. 10.
    Malmstrom, R., Packard, C. J., Caslake, M., et al. (1997). Defective regulation of triglyceride metabolism by insulin in the liver in NIDDM. Diabetologia, 40(4), 454–462.CrossRefPubMedGoogle Scholar
  11. 11.
    Goldberg, I. J., & Merkel, M. (2001). Lipoprotein lipase: Physiology, biochemistry, and molecular biology. Frontiers in Bioscience: A Journal and Virtual Library, 6, D388–405.CrossRefGoogle Scholar
  12. 12.
    Bamba, V., & Rader, D. J. (2007). Obesity and atherogenic dyslipidemia. Gastroenterology, 132(6), 2181–2190.CrossRefPubMedGoogle Scholar
  13. 13.
    Merkel, M., Eckel, R. H., & Goldberg, I. J. (2002). Lipoprotein lipase: Genetics, lipid uptake, and regulation. Journal of Lipid Research, 43(12), 1997–2006.CrossRefPubMedGoogle Scholar
  14. 14.
    Ruge, T., Svensson, M., Eriksson, J. W., & Olivecrona, G. (2005). Tissue-specific regulation of lipoprotein lipase in humans: Effects of fasting. European Journal of Clinical Investigation, 35(3), 194–200.CrossRefPubMedGoogle Scholar
  15. 15.
    Yu, Y. H., & Ginsberg, H. N. (2005). Adipocyte signaling and lipid homeostasis: Sequelae of insulin-resistant adipose tissue. Circulation Research, 96(10), 1042–1052.CrossRefPubMedGoogle Scholar
  16. 16.
    Panarotto, D., Remillard, P., Bouffard, L., & Maheux, P. (2002). Insulin resistance affects the regulation of lipoprotein lipase in the postprandial period and in an adipose tissue-specific manner. European Journal of Clinical Investigation, 32(2), 84–92.CrossRefPubMedGoogle Scholar
  17. 17.
    Large, V., Peroni, O., Letexier, D., Ray, H., & Beylot, M. (2004). Metabolism of lipids in human white adipocyte. Diabetes & Metabolism, 30(4), 294–309.CrossRefGoogle Scholar
  18. 18.
    Bagnato, C., & Igal, R. A. (2003). Overexpression of diacylglycerol acyltransferase-1 reduces phospholipid synthesis, proliferation, and invasiveness in simian virus 40-transformed human lung fibroblasts. The Journal of Biological Chemistry, 278(52), 52203–52211.CrossRefPubMedGoogle Scholar
  19. 19.
    Smith, S. J., Cases, S., Jensen, D. R., et al. (2000). Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nature Genetics, 25(1), 87–90.CrossRefPubMedGoogle Scholar
  20. 20.
    Chen, H. C., Smith, S. J., Ladha, Z., et al. (2002). Increased insulin and leptin sensitivity in mice lacking acyl CoA: Diacylglycerol acyltransferase 1. The Journal of Clinical Investigation, 109(8), 1049–1055.PubMedGoogle Scholar
  21. 21.
    Stone, S. J., Myers, H. M., Watkins, S. M., et al. (2004). Lipopenia and skin barrier abnormalities in DGAT2-deficient mice. The Journal of Biological Chemistry, 279(12), 11767–11776.CrossRefPubMedGoogle Scholar
  22. 22.
    Oelkers, P., Behari, A., Cromley, D., Billheimer, J. T., & Sturley, S. L. (1998). Characterization of two human genes encoding acyl coenzyme A: Cholesterol acyltransferase-related enzymes. The Journal of Biological Chemistry, Oct 9 273(41), 26765–26771.CrossRefPubMedGoogle Scholar
  23. 23.
    Cases, S., Stone, S. J., Zhou, P., et al. (2001). Cloning of DGAT2, a second mammalian diacylglycerol acyltransferase, and related family members. The Journal of Biological Chemistry, 276(42), 38870–38876.CrossRefPubMedGoogle Scholar
  24. 24.
    Meegalla, R. L., Billheimer, J. T., & Cheng, D. (2002). Concerted elevation of acyl-coenzyme A: Diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin. Biochemical and Biophysical Research Communications, 298(3), 317–323.CrossRefPubMedGoogle Scholar
  25. 25.
    Yen, C. L., Monetti, M., Burri, B. J., & Farese, R. V., Jr. (2005). The triacylglycerol synthesis enzyme DGAT1 also catalyzes the synthesis of diacylglycerols, waxes, and retinyl esters. Journal of Lipid Research, 46(7), 1502–1511.CrossRefPubMedGoogle Scholar
  26. 26.
    Orland, M. D., Anwar, K., Cromley, D., et al. (2005). Acyl coenzyme A dependent retinol esterification by acyl coenzyme A: Diacylglycerol acyltransferase 1. Biochimica et Biophysica Acta, 1737(1), 76–82.PubMedGoogle Scholar
  27. 27.
    Chen, H. C., & Farese, R. V., Jr. (2000). DGAT and triglyceride synthesis: A new target for obesity treatment? Trends in Cardiovascular Medicine, 10(5), 188–192.CrossRefPubMedGoogle Scholar
  28. 28.
    Haemmerle, G., Zimmermann, R., & Zechner, R. (2003). Letting lipids go: Hormone-sensitive lipase. Current Opinion in Lipidology, 14(3), 289–297.CrossRefPubMedGoogle Scholar
  29. 29.
    Langin, D. (2006). Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome. Pharmacological Research, 53(6), 482–491.CrossRefPubMedGoogle Scholar
  30. 30.
    Skowronski, R., Hollenbeck, C. B., Varasteh, B. B., Chen, Y. D., & Reaven, G. M. (1991). Regulation of non-esterified fatty acid and glycerol concentration by insulin in normal individuals and patients with type 2 diabetes. Diabetic Medicine: A Journal of the British Diabetic Association, 8(4), 330–333.Google Scholar
  31. 31.
    Zimmermann, R., Strauss, J. G., Haemmerle, G., et al. (2004). Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science, 306(5700), 1383–1386.CrossRefPubMedGoogle Scholar
  32. 32.
    Kershaw, E. E., Hamm, J. K., Verhagen, L. A., Peroni, O., Katic, M., & Flier, J. S. (2006). Adipose triglyceride lipase: Function, regulation by insulin, and comparison with adiponutrin. Diabetes, 55(1), 148–157.CrossRefPubMedGoogle Scholar
  33. 33.
    Kershaw, E. E., Schupp, M., Guan, H. P., Gardner, N. P., Lazar, M. A., & Flier, J. S. (2007). PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. American Journal of Physiology. Endocrinology and Metabolism, 293(6), E1736–1745.CrossRefPubMedGoogle Scholar
  34. 34.
    Towler, M. C., & Hardie, D. G. (2007). AMP-activated protein kinase in metabolic control and insulin signaling. Circulation Research, 100(3), 328–341.CrossRefPubMedGoogle Scholar
  35. 35.
    Brooks, B. J., Arch, J. R., & Newsholme, E. A. (1983). Effect of some hormones on the rate of the triacylglycerol/fatty-acid substrate cycle in adipose tissue of the mouse in vivo. Bioscience Reports, 3(3), 263–267.CrossRefPubMedGoogle Scholar
  36. 36.
    Hardie, D. G., & Carling, D. (1997). The AMP-activated protein kinase–fuel gauge of the mammalian cell? European Journal of Biochemistry/FEBS, 246(2), 259–273.CrossRefPubMedGoogle Scholar
  37. 37.
    Yamauchi, T., Kamon, J., Minokoshi, Y., et al. (2002). Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nature Medicine, 8(11), 1288–1295.CrossRefPubMedGoogle Scholar
  38. 38.
    Tunaru, S., Kero, J., Schaub, A., et al. (2003). PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti- lipolytic effect. Nature Medicine, 9(3), 352–355.CrossRefPubMedGoogle Scholar
  39. 39.
    Offermanns, S. (2006). The nicotinic acid receptor GPR109A (HM74A or PUMA-G) as a new therapeutic target. Trends in Pharmacological Sciences, 27(7), 384–390.CrossRefPubMedGoogle Scholar
  40. 40.
    Karpe, F., & Frayn, K. N. (2004). The nicotinic acid receptor – a new mechanism for an old drug. Lancet, 363(9424), 1892–1894.CrossRefPubMedGoogle Scholar
  41. 41.
    Pike, N. B., & Wise, A. (2004). Identification of a nicotinic acid receptor: Is this the molecular target for the oldest lipid-lowering drug? Current Opinion in Investigational Drugs (London, England: 2000), 5(3), 271–275.Google Scholar
  42. 42.
    Taggart, A. K., Kero, J., Gan, X., et al. (2005). (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. The Journal of Biological Chemistry, 280(29), 26649–26652.CrossRefPubMedGoogle Scholar
  43. 43.
    Wise, A., Foord, S. M., Fraser, N. J., et al. (2003). Molecular identification of high and low affinity receptors for nicotinic acid. The Journal of Biological Chemistry, 278(11), 9869–9874.CrossRefPubMedGoogle Scholar
  44. 44.
    Wu, X., Motoshima, H., Mahadev, K., Stalker, T. J., Scalia, R., & Goldstein, B. J. (2003). Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes, 52(6), 1355–1363.CrossRefPubMedGoogle Scholar
  45. 45.
    Westphal, S., Borucki, K., Taneva, E., Makarova, R., & Luley, C. (2006). Adipokines and treatment with niacin. Metabolism: Clinical and Experimental, 55(10), 1283–1285.Google Scholar
  46. 46.
    Schoonjans, K., Staels, B., & Auwerx, J. (1996). Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. Journal of Lipid Research, 37(5), 907–925.PubMedGoogle Scholar
  47. 47.
    Li, P., Zhu, Z., Lu, Y., & Granneman, J. G. (2005). Metabolic and cellular plasticity in white adipose tissue II: Role of peroxisome proliferator-activated receptor-alpha. American Journal of Physiology. Endocrinology and Metabolism, 289(4), E617–626.CrossRefPubMedGoogle Scholar
  48. 48.
    Yki-Jarvinen, H. (2004). Thiazolidinediones. The New England Journal of Medicine, 351(11), 1106–1118.CrossRefPubMedGoogle Scholar
  49. 49.
    Combs, T. P., Pajvani, U. B., Berg, A. H., et al. (2004). A transgenic mouse with a deletion in the collagenous domain of adiponectin displays elevated circulating adiponectin and improved insulin sensitivity. Endocrinology, 145(1), 367–383.CrossRefPubMedGoogle Scholar
  50. 50.
    Trujillo, M. E., & Scherer, P. E. (2005). Adiponectin – journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. Journal of Internal Medicine, 257(2), 167–175.CrossRefPubMedGoogle Scholar
  51. 51.
    Szapary, P. O., Bloedon, L. T., Samaha, F. F., et al. (2006). Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome. Arteriosclerosis, Thrombosis, and Vascular Biology, 26(1), 182–188.CrossRefPubMedGoogle Scholar
  52. 52.
    Moller, D. E., & Berger, J. P. Role of PPARs in the regulation of obesity-related insulin ­sensitivity and inflammation. International Journal of Obesity and Related Metabolic Disorders: Journal of the International Association for the Study of Obesity, 27(Suppl 3), S17–21.Google Scholar
  53. 53.
    Duffy, D., & Rader, D. (2007). Endocannabinoid antagonism: Blocking the excess in the treatment of high-risk abdominal obesity. Trends in Cardiovascular Medicine, 17(2), 35–43.CrossRefPubMedGoogle Scholar
  54. 54.
    Li, S., Brown, M. S., & Goldstein, J. L. (2010). Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proceedings of the National Academy of Sciences of the United States of America, 107(8), 3441–3446.CrossRefPubMedGoogle Scholar
  55. 55.
    Biddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., et al. (2008). Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. Cell Metabolism, 7(2), 125–134.CrossRefPubMedGoogle Scholar
  56. 56.
    Semple, R. K., Sleigh, A., Murgatroyd, P. R., et al. (2009). Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. The Journal of Clinical Investigation, 119(2), 315–322.PubMedGoogle Scholar
  57. 57.
    Taniguchi, C. M., Kondo, T., Sajan, M., et al. (2006). Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta. Cell Metabolism, 3(5), 343–353.CrossRefPubMedGoogle Scholar
  58. 58.
    Shimomura, I., Matsuda, M., Hammer, R. E., Bashmakov, Y., Brown, M. S., & Goldstein, J. L. (2000). Decreased IRS-2 and increased SREBP-1c lead to mixed insulin resistance and sensitivity in livers of lipodystrophic and ob/ob mice. Molecular Cell, 6(1), 77–86.CrossRefPubMedGoogle Scholar
  59. 59.
    Leavens, K. F., Easton, R. M., Shulman, G. I., Previs, S. F., & Birnbaum, M. J. (2009). Akt2 is required for hepatic lipid accumulation in models of insulin resistance. Cell Metabolism, 10(5), 405–418.CrossRefPubMedGoogle Scholar
  60. 60.
    Sniderman, A. D., & Cianflone, K. (1993). Substrate delivery as a determinant of hepatic apoB secretion. Arteriosclerosis and Thrombosis: A Journal of Vascular Biology/American Heart Association, 13(5), 629–636.Google Scholar
  61. 61.
    Yao, Z., & McLeod, R. S. (1994). Synthesis and secretion of hepatic apolipoprotein B-containing lipoproteins. Biochimica et Biophysica Acta, 1212(2), 152–166.PubMedGoogle Scholar
  62. 62.
    Pan, M., Maitin, V., Parathath, S., et al. (2008). Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control. Proceedings of the National Academy of Sciences, 105(15), 5862–5867.CrossRefGoogle Scholar
  63. 63.
    Ota, T., Gayet, C., & Ginsberg, H. N. (2008). Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents. The Journal of Clinical Investigation, 118(1), 316–332.CrossRefPubMedGoogle Scholar
  64. 64.
    Leung, G. K., Veniant, M. M., Kim, S. K., et al. (2000). A deficiency of microsomal triglyceride transfer protein reduces apolipoprotein B secretion. Journal of Biological Chemistry, 275(11), 7515–7520.CrossRefPubMedGoogle Scholar
  65. 65.
    Tietge, U. J., Bakillah, A., Maugeais, C., Tsukamoto, K., Hussain, M., & Rader, D. J. (1999). Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B. Journal of Lipid Research, 40(11), 2134–2139.PubMedGoogle Scholar
  66. 66.
    Lin, M. C., Gordon, D., & Wetterau, J. R. (1995). Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: Insulin negatively regulates MTP gene expression. Journal of Lipid Research, 36(5), 1073–1081.PubMedGoogle Scholar
  67. 67.
    Gordon, D. A., & Jamil, H. (2000). Progress towards understanding the role of microsomal triglyceride transfer protein in apolipoprotein-B lipoprotein assembly. Biochimica et Biophysica Acta, 1486(1), 72–83.PubMedGoogle Scholar
  68. 68.
    Sparks, J. D., & Sparks, C. E. (1994). Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion. Biochimica et Biophysica Acta, 1215(1–2), 9–32.PubMedGoogle Scholar
  69. 69.
    Au, W. S., Kung, H. F., & Lin, M. C. (2003). Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: Roles of MAPKerk and MAPKp38. Diabetes, 52(5), 1073–1080.CrossRefPubMedGoogle Scholar
  70. 70.
    Fredenrich, A. (1998). Role of apolipoprotein CIII in triglyceride-rich lipoprotein metabolism­. Diabetes & Metabolism, 24(6), 490–495.Google Scholar
  71. 71.
    Chen, M., Breslow, J. L., Li, W., & Leff, T. (1994). Transcriptional regulation of the apoC-III gene by insulin in diabetic mice: Correlation with changes in plasma triglyceride levels. Journal of Lipid Research, 35(11), 1918–1924.PubMedGoogle Scholar
  72. 72.
    Chan, D. C., Nguyen, M. N., Watts, G. F., & Barrett, P. H. (2008). Plasma apolipoprotein C-III transport in centrally obese men: Associations with very low-density lipoprotein apolipoprotein B and high-density lipoprotein apolipoprotein A-I metabolism. The Journal of Clinical Endocrinology and Metabolism, 93(2), 557–564.CrossRefPubMedGoogle Scholar
  73. 73.
    Duvillard, L., Pont, F., Florentin, E., Galland-Jos, C., Gambert, P., & Verges, B. (2000). Metabolic abnormalities of apolipoprotein B-containing lipoproteins in non-insulin-dependent diabetes: A stable isotope kinetic study. European Journal of Clinical Investigation, 30(8), 685–694.CrossRefPubMedGoogle Scholar
  74. 74.
    Despres, J. P., Couillard, C., Gagnon, J., et al. (2000). Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: The Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(8), 1932–1938.PubMedGoogle Scholar
  75. 75.
    Carr, M. C., Ayyobi, A. F., Murdoch, S. J., Deeb, S. S., & Brunzell, J. D. (2002). Contribution of hepatic lipase, lipoprotein lipase, and cholesteryl ester transfer protein to LDL and HDL heterogeneity in healthy women. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(4), 667–673.CrossRefPubMedGoogle Scholar
  76. 76.
    Rashid, S., Uffelman, K. D., & Lewis, G. F. (2002). The mechanism of HDL lowering in hypertriglyceridemic, insulin-resistant states. Journal of Diabetes and Its Complications, 16(1), 24–28.CrossRefPubMedGoogle Scholar
  77. 77.
    Lewis, G. F., Murdoch, S., Uffelman, K., et al. (2004). Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone. Diabetes, 53(11), 2893–2900.CrossRefPubMedGoogle Scholar
  78. 78.
    Rosenson, R. S. (2004). Statins in atherosclerosis: Lipid-lowering agents with antioxidant capabilities. Atherosclerosis, 173(1), 1–12.CrossRefPubMedGoogle Scholar
  79. 79.
    Goldberg, I. J. (1996). Lipoprotein lipase and lipolysis: Central roles in lipoprotein metabolism and atherogenesis. Journal of Lipid Research, 37(4), 693–707.PubMedGoogle Scholar
  80. 80.
    Lewis, G. F., & Rader, D. J. (2005). New insights into the regulation of HDL metabolism and reverse cholesterol transport. Circulation Research, 96(12), 1221–1232.CrossRefPubMedGoogle Scholar
  81. 81.
    Dullaart, R. P., Sluiter, W. J., Dikkeschei, L. D., Hoogenberg, K., & Van Tol, A. (1994). Effect of adiposity on plasma lipid transfer protein activities: A possible link between insulin resistance and high density lipoprotein metabolism. European Journal of Clinical Investigation, 24(3), 188–194.CrossRefPubMedGoogle Scholar
  82. 82.
    MacLean, P. S., Vadlamudi, S., MacDonald, K. G., Pories, W. J., & Barakat, H. A. (2005). Suppression of hepatic cholesteryl ester transfer protein expression in obese humans with the development of type 2 diabetes mellitus. The Journal of Clinical Endocrinology and Metabolism, 90(4), 2250–2258.CrossRefPubMedGoogle Scholar
  83. 83.
    Remillard, P., Shen, G., Milne, R., & Maheux, P. (2001). Induction of cholesteryl ester transfer protein in adipose tissue and plasma of the fructose-fed hamster. Life Sciences, 69(6), 677–687.CrossRefPubMedGoogle Scholar
  84. 84.
    Blades, B., Vega, G. L., & Grundy, S. M. (1993). Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol. Arterioscler Thromb, 13(8), 1227–1235.PubMedGoogle Scholar
  85. 85.
    Despres, J. P., Ferland, M., Moorjani, S., et al. (1989). Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. Arteriosclerosis (Dallas, Tex.), 9(4), 485–492.Google Scholar
  86. 86.
    Rashid, S., Barrett, P. H., Uffelman, K. D., Watanabe, T., Adeli, K., & Lewis, G. F. (2002). Lipolytically modified triglyceride-enriched HDLs are rapidly cleared from the circulation. Arteriosclerosis, Thrombosis, and Vascular Biology, 22(3), 483–487.CrossRefPubMedGoogle Scholar
  87. 87.
    Lewis, G. F., Lamarche, B., Uffelman, K. D., et al. (1997). Clearance of postprandial and lipolytically modified human HDL in rabbits and rats. Journal of Lipid Research, 38(9), 1771–1778.PubMedGoogle Scholar
  88. 88.
    Lewis, G. F., Murdoch, S., Uffelman, K., et al. (2004). Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone. Diabetes, 53(11), 2893–2900.CrossRefPubMedGoogle Scholar
  89. 89.
    Badellino, K. O., Wolfe, M. L., Reilly, M. P., & Rader, D. J. (2006). Endothelial lipase ­concentrations are increased in metabolic syndrome and associated with coronary atherosclerosis. PLoS Medicine, 3(2), e22.CrossRefPubMedGoogle Scholar
  90. 90.
    Ishida, T., Choi, S., Kundu, R. K., et al. (2003). Endothelial lipase is a major determinant of HDL level. The Journal of Clinical Investigation, 111(3), 347–355.PubMedGoogle Scholar
  91. 91.
    Jaye, M., Lynch, K. J., Krawiec, J., et al. (1999). A novel endothelial-derived lipase that modulates HDL metabolism. Nature Genetics, 21(4), 424–428.CrossRefPubMedGoogle Scholar
  92. 92.
    Maugeais, C., Tietge, U. J., Broedl, U. C., et al. (2003). Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipase. Circulation, 108(17), 2121–2126.CrossRefPubMedGoogle Scholar
  93. 93.
    Jin, W., Millar, J. S., Broedl, U., Glick, J. M., & Rader, D. J. (2003). Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. The Journal of Clinical Investigation, 111(3), 357–362.PubMedGoogle Scholar
  94. 94.
    Ma, K., Cilingiroglu, M., Otvos, J. D., Ballantyne, C. M., Marian, A. J., & Chan, L. (2003). Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. Proceedings of the National Academy of Sciences of the United States of America, 100(5), 2748–2753.CrossRefPubMedGoogle Scholar
  95. 95.
    deLemos, A. S., Wolfe, M. L., Long, C. J., Sivapackianathan, R., & Rader, D. J. (2002). Identification of genetic variants in endothelial lipase in persons with elevated high-density lipoprotein cholesterol. Circulation, 106(11), 1321–1326.CrossRefPubMedGoogle Scholar
  96. 96.
    Zhang, Y., McGillicuddy, F. C., Hinkle, C. C., et al. Adipocyte modulation of high-density lipoprotein cholesterol. Circulation, 121(11), 1347–1355.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of MedicineNational University of SingaporeSingaporeSingapore

Personalised recommendations