Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 340731, 17 pages
http://dx.doi.org/10.1155/2013/340731
Research Article

Hepatic Gene Expression Profiling in Nrf2 Knockout Mice after Long-Term High-Fat Diet-Induced Obesity

1Division of Endocrinology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece
2Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA
3Laboratory of Virology, Medical School, University of Crete, 71110 Heraklion, Greece
4Department of Biological Sciences, Molecular Medicine Research Center and Laboratory of Molecular and Medical Genetics, University of Cyprus, 1678 Nicosia, Cyprus

Received 9 January 2013; Revised 5 March 2013; Accepted 9 March 2013

Academic Editor: Jingbo Pi

Copyright © 2013 Dionysios V. Chartoumpekis et al. 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. S. Haffner and H. Taegtmeyer, “Epidemic obesity and the metabolic syndrome,” Circulation, vol. 108, no. 13, pp. 1541–1545, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. P. T. James, R. Leach, E. Kalamara, and M. Shayeghi, “The worldwide obesity epidemic,” Obesity Research, vol. 9, supplement 4, pp. 228S–233S, 2001. View at Google Scholar
  3. E. E. Calle and R. Kaaks, “Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms,” Nature Reviews Cancer, vol. 4, no. 8, pp. 579–591, 2004. View at Google Scholar · View at Scopus
  4. R. N. Bergman, S. P. Kim, I. R. Hsu et al., “Abdominal obesity: role in the pathophysiology of metabolic disease and cardiovascular risk,” American Journal of Medicine, vol. 120, no. 2, supplement 1, pp. 3–8, 2007. View at Google Scholar
  5. G. P. Sykiotis, I. G. Habeos, A. V. Samuelson, and D. Bohmann, “The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation,” Current Opinion in Clinical Nutrition and Metabolic Care, vol. 14, no. 1, pp. 41–48, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. M. J. Calkins, D. A. Johnson, J. A. Townsend et al., “The Nrf2/ARE pathway as a potential therapeutic target in neurodegenerative disease,” Antioxidants and Redox Signaling, vol. 11, no. 3, pp. 497–508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. M. Kobayashi and M. Yamamoto, “Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species,” Advances in Enzyme Regulation, vol. 46, no. 1, pp. 113–140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. G. P. Sykiotis and D. Bohmann, “Stress-activated cap'n'collar transcription factors in aging and human disease,” Science Signaling, vol. 3, no. 112, p. re3, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. T. W. Kensler, N. Wakabayashi, and S. Biswal, “Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway,” Annual Review of Pharmacology and Toxicology, vol. 47, pp. 89–116, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. W. O. Osburn and T. W. Kensler, “Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults,” Mutation Research, vol. 659, no. 1-2, pp. 31–39, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. J. M. Lee, J. Li, D. A. Johnson et al., “Nrf2, a multi-organ protector?” FASEB Journal, vol. 19, no. 9, pp. 1061–1066, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Motohashi and M. Yamamoto, “Nrf2-Keap1 defines a physiologically important stress response mechanism,” Trends in Molecular Medicine, vol. 10, no. 11, pp. 549–557, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. D. V. Chartoumpekis, P. G. Ziros, A. I. Psyrogiannis et al., “Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice,” Diabetes, vol. 60, no. 10, pp. 2465–2473, 2011. View at Google Scholar
  14. J. Pi, L. Leung, P. Xue et al., “Deficiency in the nuclear factor E2-related factor-2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity,” Journal of Biological Chemistry, vol. 285, no. 12, pp. 9292–9300, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. K. Zhang, K. C. Wu, J. Liu, and C. D. Klaassen, “Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet,” Toxicology and Applied Pharmacology, vol. 264, no. 3, pp. 305–314, 2012. View at Publisher · View at Google Scholar
  16. A. K. Meher, P. R. Sharma, V. A. Lira et al., “Nrf2 deficiency in myeloid cells is not sufficient to protect mice from high-fat diet-induced adipose tissue inflammation and insulin resistance,” Free Radical Biology & Medicine, vol. 52, no. 9, pp. 1708–1715, 2012. View at Publisher · View at Google Scholar
  17. K. Itoh, T. Chiba, S. Takahashi et al., “An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements,” Biochemical and Biophysical Research Communications, vol. 236, no. 2, pp. 313–322, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. A. I. Saeed, N. K. Bhagabati, J. C. Braisted et al., “TM4 microarray software suite,” Methods in Enzymology, vol. 411, pp. 134–193, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. A. I. Saeed, V. Sharov, J. White et al., “TM4: a free, open-source system for microarray data management and analysis,” BioTechniques, vol. 34, no. 2, pp. 374–378, 2003. View at Google Scholar · View at Scopus
  20. B. Zhang, S. Kirov, and J. Snoddy, “WebGestalt: an integrated system for exploring gene sets in various biological contexts,” Nucleic Acids Research, vol. 33, no. 2, pp. W741–W748, 2005. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Zaravinos, G. I. Lambrou, I. Boulalas, D. Delakas, and D. A. Spandidos, “Identification of common differentially expressed genes in urinary bladder cancer,” PLoS ONE, vol. 6, no. 4, Article ID e18135, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. M. W. Pfaffl, “A new mathematical model for relative quantification in real-time RT-PCR,” Nucleic Acids Research, vol. 29, no. 9, article e45, 2001. View at Google Scholar · View at Scopus
  23. A. Spandidos, X. Wang, H. Wang, S. Dragnev, T. Thurber, and B. Seed, “A comprehensive collection of experimentally validated primers for Polymerase Chain Reaction quantitation of murine transcript abundance,” BMC Genomics, vol. 9, article 633, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Spandidos, X. Wang, H. Wang, and B. Seed, “PrimerBank: a resource of human and mouse PCR primer pairs for gene expression detection and quantification,” Nucleic Acids Research, vol. 38, no. 1, pp. D792–D799, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. X. Wang and B. Seed, “A PCR primer bank for quantitative gene expression analysis,” Nucleic Acids Research, vol. 31, no. 24, article e154, 2003. View at Publisher · View at Google Scholar
  26. Y. Zhang, X. Cheng, L. Aleksunes, and C. D. Klaassen, “Transcription factor-mediated regulation of carboxylesterase enzymes in livers of mice,” Drug Metabolism and Disposition, vol. 40, no. 6, pp. 1191–1197, 2012. View at Google Scholar
  27. J. D. Hayes, S. A. Chanas, C. J. Henderson et al., “The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin,” Biochemical Society Transactions, vol. 28, no. 2, pp. 33–41, 2000. View at Google Scholar · View at Scopus
  28. M. S. Yates, M. K. Kwak, P. A. Egner et al., “Potent protection against aflatoxin-induced tumorigenesis through induction of Nrf2-regulated pathways by the triterpenoid 1-[2-cyano-3-,12-dioxooleana-1, 9(11)-dien-28-oyl]imidazole,” Cancer Research, vol. 66, no. 4, pp. 2488–2494, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. P. Nioi, M. McMahon, K. Itoh, M. Yamamoto, and J. D. Hayes, “Identification of a novel NRF2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence,” Biochemical Journal, vol. 374, no. 2, pp. 337–348, 2003. View at Publisher · View at Google Scholar · View at Scopus
  30. R. K. Thimmulappa, H. Lee, T. Rangasamy et al., “Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis,” Journal of Clinical Investigation, vol. 116, no. 4, pp. 984–995, 2006. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Itoh, M. Mochizuki, Y. Ishii et al., “Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-Δ12,14-prostaglandin j(2),” Molecular and Cellular Biology, vol. 24, no. 1, pp. 36–45, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. N. G. Innamorato, A. I. Rojo, Á. J. García-Yagüe, M. Yamamoto, M. L. De Ceballos, and A. Cuadrado, “The transcription factor nrf2 is a therapeutic target against brain inflammation,” Journal of Immunology, vol. 181, no. 1, pp. 680–689, 2008. View at Google Scholar · View at Scopus
  33. N. Li and A. E. Nel, “Role of the Nrf2-mediated signaling pathway as a negative regulator of inflammation: implications for the impact of particulate pollutants on asthma,” Antioxidants and Redox Signaling, vol. 8, no. 1-2, pp. 88–98, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. S. A. Chanas, Q. Jiang, M. McMahon et al., “Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice,” Biochemical Journal, vol. 365, no. 2, pp. 405–416, 2002. View at Publisher · View at Google Scholar · View at Scopus
  35. R. K. Thimmulappa, K. H. Mai, S. Srisuma, T. W. Kensler, M. Yamamoto, and S. Biswal, “Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray,” Cancer Research, vol. 62, no. 18, pp. 5196–5203, 2002. View at Google Scholar · View at Scopus
  36. Y. Tanaka, L. M. Aleksunes, R. L. Yeager et al., “NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet,” Journal of Pharmacology and Experimental Therapeutics, vol. 325, no. 2, pp. 655–664, 2008. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. K. J. Zhang, G. L. Guo, and C. D. Klaassen, “Diurnal variations of mouse plasma and hepatic bile acid concentrations as well as expression of biosynthetic enzymes and transporters,” PLoS ONE, vol. 6, no. 2, Article ID e16683, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Huang, I. Tabbi-Anneni, V. Gunda, and L. Wang, “Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism,” American Journal of Physiology, vol. 299, no. 6, pp. G1211–G1221, 2010. View at Publisher · View at Google Scholar · View at Scopus
  39. W. F. Yiu, P. L. Kwan, C. Y. Wong et al., “Attenuation of fatty liver and prevention of hypercholesterolemia by extract of Curcuma longa through regulating the expression of CYP7A1, LDL-receptor, HO-1, and HMG-CoA reductase,” Journal of Food Science, vol. 76, no. 3, pp. H80–H89, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. G. Slegenthaler, R. Hotz, D. Chatellard-Gruaz, S. Jaconi, and J. H. Saurat, “Characterization and expression of a novel human fatty acid-binding protein: the epidermal type (E-FABP),” Biochemical and Biophysical Research Communications, vol. 190, no. 2, pp. 482–487, 1993. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Hoekstra, M. Stitzinger, E. J. A. Van Wanrooij et al., “Microarray analysis indicates an important role for FABP5 and putative novel FABPs on a Western-type diet,” Journal of Lipid Research, vol. 47, no. 10, pp. 2198–2207, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. A. A. Toye, M. E. Dumas, C. Blancher et al., “Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice,” Diabetologia, vol. 50, no. 9, pp. 1867–1879, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. N. R. Kitteringham, A. Abdullah, J. Walsh et al., “Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver,” Journal of Proteomics, vol. 73, no. 8, pp. 1612–1631, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. P. Wei, J. Zhang, M. Egan-Haftey, S. Liang, and D. D. Moore, “The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism,” Nature, vol. 407, no. 6806, pp. 920–923, 2000. View at Publisher · View at Google Scholar · View at Scopus
  45. T. Wada, J. Gao, and W. Xie, “PXR and CAR in energy metabolism,” Trends in Endocrinology and Metabolism, vol. 20, no. 6, pp. 273–279, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Gao, J. He, Y. Zhai, T. Wada, and W. Xie, “The constitutive androstane receptor is an anti-obesity nuclear receptor that improves in sulin sensitivity,” Journal of Biological Chemistry, vol. 284, no. 38, pp. 25984–25992, 2009. View at Publisher · View at Google Scholar · View at Scopus
  47. B. Dong, P. K. Saha, W. Huang et al., “Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 44, pp. 18831–18836, 2009. View at Google Scholar
  48. P. Honkakoski, I. Zelko, T. Sueyoshi, and M. Negishi, “The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene,” Molecular and Cellular Biology, vol. 18, no. 10, pp. 5652–5658, 1998. View at Google Scholar · View at Scopus
  49. A. Anwar-Mohamed, O. S. Degenhardt, M. A. M. El Gendy, J. M. Seubert, S. R. Kleeberger, and A. O. S. El-Kadi, “The effect of Nrf2 knockout on the constitutive expression of drug metabolizing enzymes and transporters in C57Bl/6 mice livers,” Toxicology in Vitro, vol. 25, no. 4, pp. 785–795, 2011. View at Publisher · View at Google Scholar · View at Scopus
  50. K. C. Wu, J. Y. Cui, and C. D. Klaassen, “Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver,” PLoS One, vol. 7, no. 7, Article ID e39006, 2012. View at Publisher · View at Google Scholar
  51. K. W. Cho, Y. Zhou, L. Sheng, and L. Rui, “Lipocalin-13 regulates glucose metabolism by both insulin-dependent and insulin-independent mechanisms,” Molecular and Cellular Biology, vol. 31, no. 3, pp. 450–457, 2011. View at Publisher · View at Google Scholar · View at Scopus
  52. E. M. Wintour and B. A. Henry, “Glycerol transport: an additional target for obesity therapy?” Trends in Endocrinology and Metabolism, vol. 17, no. 3, pp. 77–78, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. F. García, A. Kierbel, M. C. Larocca et al., “The water channel aquaporin-8 is mainly intracellular in rat hepatocytes, and its plasma membrane insertion is stimulated by cyclic AMP,” Journal of Biological Chemistry, vol. 276, no. 15, pp. 12147–12152, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. E. S. Pilka, F. H. Niesen, W. H. Lee et al., “Structural basis for substrate specificity in human monomeric carbonyl reductases,” PLoS ONE, vol. 4, no. 10, article e7113, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. C. Chang, P. H. Liu, Y. C. Tsai et al., “Genetic variation in the carbonyl reductase 3 gene confers risk of type 2 diabetes and insulin resistance: a potential regulator of adipogenesis,” Journal of Molecular Medicine, vol. 90, no. 7, pp. 847–858, 2012. View at Google Scholar
  56. Q. Cheng, J. L. Kalabus, J. Zhang, and J. G. Blanco, “A conserved antioxidant response element (ARE) in the promoter of human carbonyl reductase 3 (CBR3) mediates induction by the master redox switch Nrf2,” Biochemical Pharmacology, vol. 83, no. 1, pp. 139–148, 2012. View at Publisher · View at Google Scholar
  57. B. Ebert, M. Kisiela, P. Malátková, Y. El-Hawari, and E. Maser, “Regulation of human carbonyl reductase 3 (CBR3; SDR21C2) expression by Nrf2 in cultured cancer cells,” Biochemistry, vol. 49, no. 39, pp. 8499–8511, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Hu, C. Xu, G. Shen et al., “Gene expression profiles induced by cancer chemopreventive isothiocyanate sulforaphane in the liver of C57BL/6J mice and C57BL/6J/Nrf2 (-/-) mice,” Cancer Letters, vol. 243, no. 2, pp. 170–192, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Hu, C. Xu, G. Shen et al., “Identification of Nrf2-regulated genes induced by chemopreventive isothiocyanate PEITC by oligonucleotide microarray,” Life Sciences, vol. 79, no. 20, pp. 1944–1955, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Mitsuishi, K. Taguchi, Y. Kawatani et al., “Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming,” Cancer Cell, vol. 22, no. 1, pp. 66–79, 2012. View at Google Scholar
  61. M. A. Lazar and M. J. Birnbaum, “Physiology. De-meaning of metabolism,” Science, vol. 336, no. 6089, pp. 1651–1652, 2012. View at Publisher · View at Google Scholar