Journal of Clinical Lipidology
Volume 2, Issue 4 , Pages 279-284 , August 2008

Analysis of 6-month effect of orlistat administration, alone or in combination with fenofibrate, on triglyceride-rich lipoprotein metabolism in overweight and obese patients with metabolic syndrome

  • Theodosios D. Filippatos, MD

      Affiliations

    • Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Vasilis Tsimihodimos, MD

      Affiliations

    • Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Michael Kostapanos, MD

      Affiliations

    • Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Christina Kostara, PhD

      Affiliations

    • Laboratory of Clinical Chemistry, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Eleni T. Bairaktari, PhD

      Affiliations

    • Laboratory of Clinical Chemistry, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Dimitrios N. Kiortsis, MD

      Affiliations

    • Laboratory of Physiology, Medical School, University of Ioannina, 45 110 Ioannina, Greece
    • ,
  • Moses S. Elisaf, MD

      Affiliations

    • Department of Internal Medicine, School of Medicine, University of Ioannina, 45 110 Ioannina, Greece
    • Corresponding Author InformationCorresponding author.

Received 16 January 2008 ,Accepted 8 June 2008.

References 

  1. Kiortsis DN, Filippatos TD, Elisaf MS. The effects of orlistat on metabolic parameters and other cardiovascular risk factors. Diabetes Metab. 2005;31:15–22
  2. Muls E, Kolanowski J, Scheen A, Van Gaal L. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes Relat Metab Disord. 2001;25:1713–1721
  3. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235–242
  4. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes (A 1-year randomized double-blind study). Diabetes Care. 1998;21:1288–1294
  5. Sjostrom L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients (European Multicentre Orlistat Study Group). Lancet. 1998;352:167–172
  6. Torgerson JS, Hauptman J, Boldrin MN, Sjostrom L. XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27:155–161
  7. Derosa G, Mugellini A, Ciccarelli L, Fogari R. Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both an anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet. Clin Ther. 2003;25:1107–1122
  8. Elisaf M. Effects of fibrates on serum metabolic parameters. Curr Med Res Opin. 2002;18:269–276
  9. Tsimihodimos V, Miltiadous G, Daskalopoulou SS, Mikhailidis DP, Elisaf MS. Fenofibrate: metabolic and pleiotropic effects. Curr Vasc Pharmacol. 2005;3:87–98
  10. Andersson Y, Majd Z, Lefebvre AM, et al. Developmental and pharmacological regulation of apolipoprotein C-II gene expression (Comparison with apo C-I and apo C-III gene regulation). Arterioscler Thromb Vasc Biol. 1999;19:115–121
  11. Haubenwallner S, Essenburg AD, Barnett BC, et al. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: a potential physiologic basis for their mode of action. J Lipid Res. 1995;36:2541–2551
  12. Fruchart JC, Duriez P. Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism. Drugs Today (Barc). 2006;42:39–64
  13. Jong MC, Hofker MH, Havekes LM. Role of ApoCs in lipoprotein metabolism: functional differences between ApoC1, ApoC2, and ApoC3. Arterioscler Thromb Vasc Biol. 1999;19:472–484
  14. Wang CS. Structure and functional properties of apolipoprotein C-II. Prog Lipid Res. 1991;30:253–258
  15. McConathy WJ, Gesquiere JC, Bass H, Tartar A, Fruchart JC, Wang CS. Inhibition of lipoprotein lipase activity by synthetic peptides of apolipoprotein C-III. J Lipid Res. 1992;33:995–1003
  16. Filippatos TD, Kiortsis DN, Liberopoulos EN, Georgoula M, Mikhailidis DP, Elisaf MS. Effect of orlistat, micronised fenofibrate and their combination on metabolic parameters in overweight and obese patients with the metabolic syndrome: the FenOrli study. Curr Med Res. Opin. 2005;21:1997–2006
  17. Filippatos TD, Gazi IF, Liberopoulos EN, et al. The effect of orlistat and fenofibrate, alone or in combination, on small dense LDL and lipoprotein-associated phospholipase A2 in obese patients with metabolic syndrome. Atherosclerosis. 2007;193:428–437
  18. Filippatos TD, Liberopoulos EN, Kostapanos M, et al. The effects of orlistat and fenofibrate, alone or in combination, on high-density lipoprotein subfractions and pre-beta1-HDL levels in obese patients with metabolic syndrome. Diabetes Obes Metab. 2008;10:476–483
  19. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report (2002). Circulation. 2002;106:3143–3421.
  20. Sakurabayashi I, Saito Y, Kita T, Matsuzawa Y, Goto Y. Reference intervals for serum apolipoproteins A-I, A-II, B, C-II, C-III, and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of sex, age, smoking, drinking, and Lp(a) level. Clin Chim Acta. 2001;312:87–95
  21. Lucas CP, Boldrin MN, Reaven GM. Effect of orlistat added to diet (30% of calories from fat) on plasma lipids, glucose, and insulin in obese patients with hypercholesterolemia. Am J Cardiol. 2003;91:961–964
  22. Reaven G, Segal K, Hauptman J, Boldrin M, Lucas C. Effect of orlistat-assisted weight loss in decreasing coronary heart disease risk in patients with syndrome X. Am J Cardiol. 2001;87:827–831
  23. Caslake MJ, Packard CJ. Phenotypes, genotypes and response to statin therapy. Curr Opin Lipidol. 2004;15:387–392
  24. Kostapanos MS, Milionis HJ, Filippatos TD, et al. A 12-week, prospective, open-label analysis of the effect of rosuvastatin on triglyceride-rich lipoprotein metabolism in patients with primary dyslipidemia. Clin Ther. 2007;29:1403–1414
  25. Bradley WA, Hwang SL, Karlin JB, et al. Low-density lipoprotein receptor binding determinants switch from apolipoprotein E to apolipoprotein B during conversion of hypertriglyceridemic very-low-density lipoprotein to low-density lipoproteins. J Biol Chem. 1984;259:14728–14735
  26. Brown SA, Via DP, Gotto AM, Bradley WA, Gianturco SH. Apolipoprotein E-mediated binding of hypertriglyceridemic very low density lipoproteins to isolated low density lipoprotein receptors detected by ligand blotting. Biochem Biophys Res Commun. 1986;139:333–340
  27. Packard CJ, Demant T, Stewart JP, et al. Apolipoprotein B metabolism and the distribution of VLDL and LDL subfractions. J Lipid Res. 2000;41:305–318
  28. Reitsma JB, Castro Cabezas M, de Bruin TW, Erkelens DW. Relationship between improved postprandial lipemia and low-density lipoprotein metabolism during treatment with tetrahydrolipstatin, a pancreatic lipase inhibitor. Metabolism. 1994;43:293–298
  29. Olivecrona G, Beisiegel U. Lipid binding of apolipoprotein CII is required for stimulation of lipoprotein lipase activity against apolipoprotein CII-deficient chylomicrons. Arterioscler Thromb Vasc Biol. 1997;17:1545–1549
  30. Verine A, Salers P, Boyer J. Effects of apoproteins C on lipoprotein lipase activity bound to rat fat cells. Am J Physiol. 1982;243:E175–E181
  31. Baggio G, Manzato E, Gabelli C, et al. Apolipoprotein C-II deficiency syndrome (Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients). J Clin Invest. 1986;77:520–527
  32. Fojo SS, Brewer HB. Hypertriglyceridaemia due to genetic defects in lipoprotein lipase and apolipoprotein C-II. J Intern Med. 1992;231:669–677
  33. Shachter NS, Hayek T, Leff T, et al. Overexpression of apolipoprotein CII causes hypertriglyceridemia in transgenic mice. J Clin Invest. 1994;93:1683–1690
  34. Ishibashi S, Murase T, Takahashi K, Mori N, Kawakami M, Takaku F. Plasma apolipoprotein CII levels in hypertriglyceridemia. Metabolism. 1986;35:781–785
  35. Schonfeld G, George PK, Miller J, Reilly P, Witztum J. Apolipoprotein C-II and C-III levels in hyperlipoproteinemia. Metabolism. 1979;28:1001–1010
  36. Kowal RC, Herz J, Weisgraber KH, Mahley RW, Brown MS, Goldstein JL. Opposing effects of apolipoproteins E and C on lipoprotein binding to low density lipoprotein receptor-related protein. J Biol Chem. 1990;265:10771–10779
  37. Clavey V, Lestavel-Delattre S, Copin C, Bard JM, Fruchart JC. Modulation of lipoprotein B binding to the LDL receptor by exogenous lipids and apolipoproteins CI, CII, CIII, and E. Arterioscler Thromb Vasc Biol. 1995;15:963–971
  38. Tsimihodimos V, Kakafika A, Tambaki AP, et al. Fenofibrate induces HDL-associated PAF-AH but attenuates enzyme activity associated with apoB-containing lipoproteins. J Lipid Res. 2003;44:927–934
  39. Insua A, Massari F, Rodriguez Moncalvo JJ, Ruben Zanchetta J, Insua AM. Fenofibrate of gemfibrozil for treatment of types IIa and IIb primary hyperlipoproteinemia: a randomized, double-blind, crossover study. Endocr Pract. 2002;8:96–101
  40. Chapman MJ. Fibrates in 2003: therapeutic action in atherogenic dyslipidaemia and future perspectives. Atherosclerosis. 2003;171:1–13
  41. Jong MC, Rensen PC, Dahlmans VE, van der Boom H, van Berkel TJ, Havekes LM. Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice. J Lipid Res. 2001;42:1578–1585
  42. Wang CS, McConathy WJ, Kloer HU, Alaupovic P. Modulation of lipoprotein lipase activity by apolipoproteins (Effect of apolipoprotein C-III). J Clin Invest. 1985;75:384–390
  43. Staels B, Vu-Dac N, Kosykh VA, et al. Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase (A potential mechanism for the hypolipidemic action of fibrates). J Clin Invest. 1995;95:705–712
  44. Fernandez ML, Metghalchi S, Vega-Lopez S, Conde-Knape K, Lohman TG, Cordero-Macintyre ZR. Beneficial effects of weight loss on plasma apolipoproteins in postmenopausal women. J Nutr Biochem. 2004;15:717–721
  45. Gervaise N, Garrigue MA, Lasfargues G, Lecomte P. Triglycerides, apo C3 and Lp B:C3 and cardiovascular risk in type II diabetes. Diabetologia. 2000;43:703–708
  46. Lee SJ, Campos H, Moye LA, Sacks FM. LDL containing apolipoprotein CIII is an independent risk factor for coronary events in diabetic patients. Arterioscler Thromb Vasc Biol. 2003;23:853–858
  47. Gerber Y, Goldbourt U, Segev S, Harats D. Indices related to apo CII and CIII serum concentrations and coronary heart disease: a case-control study. Prev Med. 2003;37:18–22
  48. Luc G, Fievet C, Arveiler D, et al. Apolipoproteins C-III and E in apoB- and non-apoB-containing lipoproteins in two populations at contrasting risk for myocardial infarction: the ECTIM studyEtude Cas Temoins sur 'Infarctus du Myocarde. J Lipid Res. 1996;37:508–517
  49. Sacks FM, Alaupovic P, Moye LA, et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 2000;102:1886–1892

PII: S1933-2874(08)00262-6

doi: 10.1016/j.jacl.2008.06.001

Journal of Clinical Lipidology
Volume 2, Issue 4 , Pages 279-284 , August 2008

Article Tools