Table of Contents Author Guidelines Submit a Manuscript
PPAR Research
Volume 2009 (2009), Article ID 483485, 6 pages
http://dx.doi.org/10.1155/2009/483485
Review Article

Peroxisome Proliferator-Activated Receptors and Hepatitis C Virus-Induced Insulin Resistance

Viropathology Unit, University of Geneva Medical Center, 1211 Geneva, Switzerland

Received 12 August 2008; Accepted 24 November 2008

Academic Editor: Lawrence Serfaty

Copyright © 2009 Francesco Negro. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. C. Dreyer, G. Krey, H. Keller, F. Givel, G. Helftenbein, and W. Wahli, “Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors,” Cell, vol. 68, no. 5, pp. 879–887, 1992. View at Publisher · View at Google Scholar
  2. S. Qin, T. Liu, V. S. Kamanna, and M. L. Kashyap, “Pioglitazone stimulates apolipoprotein A-I production without affecting HDL removal in HepG2 cells: involvement of PPAR-α,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 11, pp. 2428–2434, 2007. View at Publisher · View at Google Scholar
  3. B. Staels, N. Vu-Dac, V. A. Kosykh 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,” The Journal of Clinical Investigation, vol. 95, no. 2, pp. 705–712, 1995. View at Publisher · View at Google Scholar
  4. K. Nagashima, C. Lopez, D. Donovan et al., “Effects of the PPAR? agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus,” The Journal of Clinical Investigation, vol. 115, no. 5, pp. 1323–1332, 2005. View at Publisher · View at Google Scholar
  5. K. S. Frederiksen, E. M. Wulf, K. Wassermann, P. Sauerberg, and J. Fleckner, “Identification of hepatic transcriptional changes in insulin-resistant rats treated with peroxisome proliferator activated receptor-α agonists,” Journal of Molecular Endocrinology, vol. 30, no. 3, pp. 317–329, 2003. View at Publisher · View at Google Scholar
  6. M. A. Jay and J. Ren, “Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus,” Current Diabetes Reviews, vol. 3, no. 1, pp. 33–39, 2007. View at Publisher · View at Google Scholar
  7. G. Jiang, Q. Dallas-Yang, Z. Li et al., “Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPAR? agonists,” Diabetes, vol. 51, no. 8, pp. 2412–2419, 2002. View at Publisher · View at Google Scholar
  8. X. Li, P. A. Hansen, L. Xi, R. A. S. Chandraratna, and C. F. Burant, “Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor γ and retinoic acid X receptors,” The Journal of Biological Chemistry, vol. 280, no. 46, pp. 38317–38327, 2005. View at Publisher · View at Google Scholar
  9. J. S. Welch, M. Ricote, T. E. Akiyama, F. J. Gonzalez, and C. K. Glass, “PPARγ and PPARδ negatively regulate specific subsets of lipopolysaccharide and IFN-γ target genes in macrophages,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 11, pp. 6712–6717, 2003. View at Publisher · View at Google Scholar
  10. P. Henson, “Suppression of macrophage inflammatory responses by PPARs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 11, pp. 6295–6296, 2003. View at Publisher · View at Google Scholar
  11. R. Kleemann, P. P. Gervois, L. Verschuren, B. Staels, H. M. G. Princen, and T. Kooistra, “Fibrates down-regulate IL-1-stimulated C-reactive protein gene expression in hepatocytes by reducing nuclear p50-NFκB-C/EBP-β complex formation,” Blood, vol. 101, no. 2, pp. 545–551, 2003. View at Publisher · View at Google Scholar
  12. G. Bahtiyar, J. J. Shin, A. Aytaman, J. R. Sowers, and S. I. McFarlane, “Association of diabetes and hepatitis C infection: epidemiologic evidence and pathophysiologic insights,” Current Diabetes Reports, vol. 4, no. 3, pp. 194–198, 2004. View at Publisher · View at Google Scholar
  13. J. M. Hui, A. Sud, G. C. Farrell et al., “Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression,” Gastroenterology, vol. 125, no. 6, pp. 1695–1704, 2003. View at Publisher · View at Google Scholar
  14. R. Moucari, T. Asselah, D. Cazals-Hatem et al., “Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis,” Gastroenterology, vol. 134, no. 2, pp. 416–423, 2008. View at Publisher · View at Google Scholar
  15. M. Romero-Gómez, C. M. Fernández-Rodríguez, R. J. Andrade et al., “Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C,” Journal of Hepatology, vol. 48, no. 5, pp. 721–727, 2008. View at Publisher · View at Google Scholar
  16. M. Romero-Gómez, M. Del Mar Viloria, R. J. Andrade et al., “Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients,” Gastroenterology, vol. 128, no. 3, pp. 636–641, 2005. View at Publisher · View at Google Scholar
  17. V. Ratziu, M. Munteanu, F. Charlotte, L. Bonyhay, and T. Poynard, “Fibrogenic impact of high serum glucose in chro nic hepatitis C,” Journal of Hepatology, vol. 39, no. 6, pp. 1049–1055, 2003. View at Publisher · View at Google Scholar
  18. I. J. Hickman, E. E. Powell, J. B. Prins et al., “In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy,” Journal of Hepatology, vol. 39, no. 6, pp. 1042–1048, 2003. View at Publisher · View at Google Scholar
  19. G. Leandro, A. Mangia, J. Hui et al., “Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data,” Gastroenterology, vol. 130, no. 6, pp. 1636–1642, 2006. View at Publisher · View at Google Scholar
  20. R. D'Souza, C. A. Sabin, and G. R. Foster, “Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy,” The American Journal of Gastroenterology, vol. 100, no. 7, pp. 1509–1515, 2005. View at Publisher · View at Google Scholar
  21. H. Poustchi, F. Negro, J. Hui et al., “Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3,” Journal of Hepatology, vol. 48, no. 1, pp. 28–34, 2008. View at Publisher · View at Google Scholar
  22. T. Kawaguchi, T. Yoshida, M. Harada et al., “Hepatitis C virus down-regulates insulin receptor substrates 1 and 2 through up-regulation of suppressor of cytokine signaling 3,” American Journal of Pathology, vol. 165, no. 5, pp. 1499–1508, 2004. View at Google Scholar
  23. V. Pazienza, S. Clément, P. Pugnale et al., “The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms,” Hepatology, vol. 45, no. 5, pp. 1164–1171, 2007. View at Publisher · View at Google Scholar
  24. H. Knobler, T. Zhornicky, A. Sandler, N. Haran, Y. Ashur, and A. Schattner, “Tumor necrosis factor-α-induced insulin resistance may mediate the hepatitis C virus-diabetes association,” The American Journal of Gastroenterology, vol. 98, no. 12, pp. 2751–2756, 2003. View at Publisher · View at Google Scholar
  25. Y. Shintani, H. Fujie, H. Miyoshi et al., “Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance,” Gastroenterology, vol. 126, no. 3, pp. 840–848, 2004. View at Publisher · View at Google Scholar
  26. M. J. Walsh, J. R. Jonsson, M. M. Richardson et al., “Non-response to antiviral therapy is associated with obesity and increased hepatic expression of suppressor of cytokine signalling 3 (SOCS-3) in patients with chronic hepatitis C, viral genotype 1,” Gut, vol. 55, no. 4, pp. 529–535, 2006. View at Publisher · View at Google Scholar
  27. C. Bernsmeier, F. H. T. Duong, V. Christen et al., “Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C,” Journal of Hepatology, vol. 49, no. 3, pp. 429–440, 2008. View at Publisher · View at Google Scholar
  28. A. de Gottardi, V. Pazienza, P. Pugnale et al., “Peroxisome proliferator-activated receptor-a and -? mRNA levels are reduced in chronic hepatitis C with steatosis and genotype 3 infection,” Alimentary Pharmacology & Therapeutics, vol. 23, no. 1, pp. 107–114, 2006. View at Publisher · View at Google Scholar
  29. K. Abid, V. Pazienza, A. de Gottardi et al., “An in vitro model of hepatitis C virus genotype 3a-associated triglycerides accumulation,” Journal of Hepatology, vol. 42, no. 5, pp. 744–751, 2005. View at Publisher · View at Google Scholar
  30. S. Dharancy, M. Malapel, G. Perlemuter et al., “Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection,” Gastroenterology, vol. 128, no. 2, pp. 334–342, 2005. View at Publisher · View at Google Scholar
  31. N. Marx, B. Kehrle, K. Kohlhammer et al., “PPAR activators as antiinflammatory mediators in human T lymphocytes: implications for atherosclerosis and transplantation-associated arteriosclerosis,” Circulation Research, vol. 90, no. 6, pp. 703–710, 2002. View at Publisher · View at Google Scholar
  32. F. Negro, “Mechanisms and significance of liver steatosis in hepatitis C virus infection,” World Journal of Gastroenterology, vol. 12, no. 42, pp. 6756–6765, 2006. View at Google Scholar
  33. L. Fartoux, A. Poujol-Robert, J. Guéchot, D. Wendum, R. Poupon, and L. Serfaty, “Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C,” Gut, vol. 54, no. 7, pp. 1003–1008, 2005. View at Publisher · View at Google Scholar
  34. K. Overbeck, D. Genné, A. Golay, and F. Negro, “Pioglitazone in chronic hepatitis C not responding to pegylated interferon-α and ribavirin,” Journal of Hepatology, vol. 49, no. 2, pp. 295–298, 2008. View at Publisher · View at Google Scholar
  35. H. M. Elgouhari, K. B. Cesario, R. Lopez, and N. N. Zein, “Pioglitazone improves early virologic kinetic response to PEG IFN/RBV combination therapy in hepatitis C genotype 1 naïve pts,” Hepatology, vol. 48, no. 4, p. 383A, 2008. View at Google Scholar
  36. H. Conjeevaram, C. F. Burant, B. McKenna et al., “A randomized, double-blind, placebo-controlled study of PPAR-gamma agonist pioglitazone given in combination with peginterferon and ribavirin in patients with genotype-1 chronic hepatitis C,” Hepatology, vol. 48, no. 4, p. 384A, 2008. View at Google Scholar
  37. R. Thomssen, S. Bonk, C. Propfe, K.-H. Heermann, H. G. Kochel, and A. Uy, “Association of hepatitis C virus in human sera with β-lipoprotein,” Medical Microbiology and Immunology, vol. 181, no. 5, pp. 293–300, 1992. View at Publisher · View at Google Scholar
  38. P. André, F. Komurian-Pradel, S. Deforges et al., “Characterization of low- and very-low-density hepatitis C virus RNA-containing particles,” Journal of Virology, vol. 76, no. 14, pp. 6919–6928, 2002. View at Publisher · View at Google Scholar
  39. M. Economou, H. Milionis, S. Filis et al., “Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C,” Journal of Gastroenterology and Hepatology, vol. 23, no. 4, pp. 586–591, 2008. View at Publisher · View at Google Scholar
  40. J. del Valle, J. A. Mira, I. de los Santos et al., “Baseline serum low-density lipoprotein cholesterol levels predict response to hepatitis C virus therapy in HIV/hepatitis C virus coinfected patients,” AIDS, vol. 22, no. 8, pp. 923–930, 2008. View at Publisher · View at Google Scholar
  41. B. König, A. Koch, J. Spielmann, C. Hilgenfeld, G. I. Stangl, and K. Eder, “Activation of PPARα lowers synthesis and concentration of cholesterol by reduction of nuclear SREBP-2,” Biochemical Pharmacology, vol. 73, no. 4, pp. 574–585, 2007. View at Publisher · View at Google Scholar
  42. D. M. Nathan, P. W. Angus, and P. R. Gibson, “Hepatitis B and C virus infections and anti-tumor necrosis factor-α therapy: guidelines for clinical approach,” Journal of Gastroenterology and Hepatology, vol. 21, no. 9, pp. 1366–1371, 2006. View at Publisher · View at Google Scholar
  43. S. B. Kapadia and F. V. Chisari, “Hepatitis C virus RNA replication is regulated by host geranylgeranylation and fatty acids,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 7, pp. 2561–2566, 2005. View at Publisher · View at Google Scholar
  44. R. J. Shaw, K. A. Lamia, D. Vasquez et al., “The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin,” Science, vol. 310, no. 5754, pp. 1642–1646, 2005. View at Publisher · View at Google Scholar
  45. V. A. Koivisto, R. Pelkonen, and K. Cantell, “Effect of interferon on glucose tolerance and insulin sensitivity,” Diabetes, vol. 38, no. 5, pp. 641–647, 1989. View at Publisher · View at Google Scholar
  46. E. Imano, T. Kanda, Y. Ishigami et al., “Interferon induces insulin resistance in patients with chronic active hepatitis C,” Journal of Hepatology, vol. 28, no. 2, pp. 189–193, 1998. View at Publisher · View at Google Scholar