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Review Article

Drug metabolism alterations in nonalcoholic fatty liver disease

&
Pages 317-334 | Received 06 Jan 2011, Accepted 31 Mar 2011, Published online: 25 May 2011

References

  • Adler, M., Schaffner, F. (1979). Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 67:811–816.
  • Aitken, A. E., Richardson, T. A., Morgan, E. T. (2006). Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 46:123–149.
  • Amarapurka, D. N., Amarapurkar, A. D., Patel, N. D., Agal, S., Baigal, R., Gupte, P., et al. (2006). Nonalcoholic steatohepatitis (NASH) WITH Diabetes: predictors of liver fibrosis. Ann Hepatol 5:30–33.
  • Amarapurkar, D. N., and Patel, N. D. (2004). Clinical spectrum and natural history of non-alcoholic steatohepatitis with normal alanine aminotransferase values. Trop Gastroenterol 25:130–134.
  • Anstee, Q. M., Goldin, R. D. (2006). Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 87:1–16.
  • Baker, S. S., Baker, R. D., Liu, W., Nowak, N. J., and Zhu, L. (2010). Role of alcohol metabolism in non-alcoholic steatohepatitis. PLoS One 5:e9570.
  • Barnett, C. R., Abbott, R. A., Bailey, C. J., Flatt, P. R., Ioannides, C. (1992). Cytochrome P-450-dependent mixed-function oxidase and glutathione S-transferase activities in spontaneous obesity-diabetes. Biochem Pharmacol 43:1868–1871.
  • Barshop, N. J., Capparelli, E. V., Sirlin, C. B., Schwimmer, J. B., Lavine, J. E. (2011). Acetaminophen pharmacokinetics in children with nonalcoholic fatty liver disease. J Pediatr Gastroenterol Nutr 52:198–202.
  • Baumgardner, J. N., Shankar, K., Hennings, L., Badger, T. M., Ronis, M. J. (2008). A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet. Am J Physiol Gastrointest Liver Physiol 294:G27–G38
  • Bell, L. N., Temm, C. J., Saxena, R., Vuppalanchi, R., Schauer, P., Rabinovitz, M., et al. (2010). Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content. Ann Surg 251:1041–1048.
  • Bock, K. W. (2010). Functions and Transcriptional Regulation of Adult Human Hepatic UDP-Glucuronosyl-Transferases (UGTs): Mechanisms responsible for interindividual variation of UGT levels. Biochem Pharmacol 80:771–777.
  • Boyle, J. P., Thompson, T. J., Gregg, E. W., Barker, L. E., Williamson, D. F. (2010). Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Popul Health Metr 8:29.
  • Bravo, A. A., Sheth, S. G., Chopra, S. (2001). Liver biopsy. NEJM 344:495–500.
  • Browning, J. D., Horton, J. D. (2004). Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114:147–152.
  • Bugianesi, E., Leone, N., Vanni, E., Marchesini, G., Brunello, F., Carucci, P., et al. (2002). Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 123:134–140.
  • Chalasani, N., Gorski, J. C., Asghar, M. S., Asghar, A., Foresman, B., Hall, S. D., et al. (2003). Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis. Hepatology 37:544–550.
  • Chaudhary, I. P., Tuntaterdtum, S., McNamara, P. J., Robertson, L. W., Blouin, R. A. (1993). Effect of genetic obesity and phenobarbital treatment on the hepatic conjugation pathways. J Pharmacol Exp Ther 265:1333–1338.
  • Chen, C. H., Huang, M. H., Yang, J. C., Nien, C. K., Yang, C. C., Yeh, Y. H., et al. (2006). Prevalence and risk factors of nonalcoholic fatty liver disease in an adult population of Taiwan: metabolic significance of nonalcoholic fatty liver disease in nonobese adults. J Clin Gastroenterol 40:745–752.
  • Chen, Y., Goldstein, J. A. (2009). The transcriptional regulation of the human CYP2C genes. Curr Drug Metab 10:567–578.
  • Cheng, Q., Aleksunes, L. M., Manautou, J. E., Cherrington, N. J., Scheffer, G. L., Yamasaki, H., et al. (2008). Drug-metabolizing enzyme and transporter expression in a mouse model of diabetes and obesity. Mol Pharm 5:77–91.
  • Chowdhry, S., Nazmy, M. H., Meakin, P. J., Dinkova-Kostova, A. T., Walsh, S. V., Tsujita, T., et al. (2010). Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Radic Biol Med 48:357–371.
  • Chtioui, H., Semela, D., Ledermann, M., Zimmermann, A., Dufour, J. F. (2007). Expression and activity of the cytochrome P450 2E1 in patients with nonalcoholic steatosis and steatohepatitis. Liver Int 27:764–771.
  • Clark, J. M., Diehl, A. M. (2003). Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 289:3000–3004.
  • Corcoran, G. B., Wong, B. K. (1987). Obesity as a risk factor in drug-induced organ injury: increased liver and kidney damage by acetaminophen in the obese overfed rat. J Pharmacol Exp Ther 241:921–927.
  • Corcoran, G. B., Wong, B. K., Shum, L., Galinsky, R. E. (1987). Acetaminophen sulfation deficit in obese rats overfed an energy-dense cafeteria diet. Endocr Res 13:101–121.
  • Day, C. P., James, O. F. (1998). Steatohepatitis: a tale of two “hits”? Gastroenterology 114:842–845.
  • Delgado, J. S. (2008). Evolving trends in nonalcoholic fatty liver disease. Eur J Intern Med 19:75–82.
  • Deng, Q. G., She, H., Cheng, J. H., French, S. W., Koop, D. R., Xiong, S., et al. (2005). Steatohepatitis induced by intragastric overfeeding in mice. Hepatology 42:905–914.
  • Di, Y. M., Chow, V. D., Yang, L. P., Zhou, S. F. (2009). Structure, function, regulation and polymorphism of human cytochrome P450 2A6. Curr Drug Metab 10:754–780.
  • Dolce, C. J., Russo, M., Keller, J. E., Buckingham, J., Norton, H. J., Heniford, B. T., et al. (2009). Does liver appearance predict histopathologic findings: prospective analysis of routine liver biopsies during bariatric surgery. Surg Obes Relat Dis 5:323–328.
  • Donato, M. T., Jimenez, N., Serralta, A., Mir, J., Castell, J. V., Gomez-Lechon, M. J. (2007). Effects of steatosis on drug-metabolizing capability of primary human hepatocytes. Toxicol In Vitro 21:271–276.
  • Donato, M. T., Lahoz, A., Jimenez, N., Perez, G., Serralta, A., Mir, J., et al. (2006). Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab Dispos 34:1556–1562.
  • Dong, B., Saha, P. K., Huang, W., Chen, W., Abu-Elheiga, L. A., Wakil, S. J., et al. (2009). Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A 106:18831–18836.
  • Donnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., Parks, E. J. (2005). Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351.
  • Donthamsetty, S., Bhave, V. S., Mitra, M. S., Latendresse, J. R., Mehendale, H. M. (2008). Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPARalpha with clofibrate. Toxicol Appl Pharmacol 230:327–337.
  • Edelman, A. B., Cherala, G., Stanczyk, F. Z. (2010). Metabolism and pharmacokinetics of contraceptive steroids in obese women: a review. Contraception 82:314–323.
  • Ellis, K. J. (1997). Body composition of a young, multiethnic, male population. Am J Clin Nutr 66:1323–1331.
  • Emery, M. G., Fisher, J. M., Chien, J. Y., Kharasch, E. D., Dellinger, E. P., Kowdley, K. V., et al. (2003). CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease. Hepatology 38:428–435.
  • Enriquez, A., Leclercq, I., Farrell, G. C., Robertson, G. (1999). Altered expression of hepatic CYP2E1 and CYP4A in obese, diabetic ob/ob mice, and fa/fa Zucker rats. Biochem Biophys Res Commun 255:300–306.
  • Estep, J. M., Baranova, A., Hossain, N., Elariny, H., Ankrah, K., Afendy, A., et al. (2009). Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis. Obes Surg 19:617–624.
  • Finn, R. D., Henderson, C. J., Scott, C. L., Wolf, C. R. (2009). Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway. Biochem J 417:43–54.
  • Fisher, C. D., Jackson, J. P., Lickteig, A. J., Augustine, L. M., Cherrington, N. J. (2008). Drug metabolizing enzyme induction pathways in experimental non-alcoholic steatohepatitis. Arch Toxicol 82:959–964.
  • Fisher, C. D., Lickteig, A. J., Augustine, L. M., Ranger-Moore, J., Jackson, J. P., Ferguson, S. S., et al. (2009). Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 37:2087–2094.
  • Flegal, K. M., Carroll, M. D., Kuczmarski, R. J., Johnson, C. L. (1998). Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord 22:39–47.
  • Flegal, K. M., Carroll, M. D., Ogden, C. L., Curtin, L. R. (2010). Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303:235–241.
  • Flegal, K. M., Carroll, M. D., Ogden, C. L., Johnson, C. L. (2002). Prevalence and trends in obesity among US adults, 1999–2000. JAMA 288:1723–1727.
  • Ford, E. S., Giles, W. H., Dietz, W. H. (2002). Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA 287:356–359.
  • Foucher, J., Castera, L., Bernard, P. H., Adhoute, X., Laharie, D., Bertet, J., et al. (2006). Prevalence and factors associated with failure of liver stiffness measurement using FibroScan in a prospective study of 2114 examinations. Eur J Gastroenterol Hepatol 18:411–412.
  • Fracanzani, A. L., Valenti, L., Bugianesi, E., Andreoletti, M., Colli, A., Vanni, E., et al. (2008). Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 48:792–798.
  • Gao, J., He, J., Zhai, Y., Wada, T., Xie, W. (2009). The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem 284:25984–25992.
  • Gao, J., Xie, W. (2010). Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism. Drug Metab Dispos 38:2091–2095.
  • Garg, R., Gupta, S., Maru, G. B. (2008). Dietary curcumin modulates transcriptional regulators of phase I and phase II Enzymes in benzo[a]pyrene-treated mice: mechanism of its anti-initiating action. Carcinogenesis 29:1022–1032.
  • Gomez-Lechon, M. J., Jover, R., Donato, M. T. (2009). Cytochrome P450 and steatosis. Curr Drug Metab 10:692–699.
  • Gonzalez, F. J. (2007). The 2006 Bernard B. Brodie Award Lecture. Cyp2e1. Drug Metab Dispos 35:1–8.
  • Greco, D., Kotronen, A., Westerbacka, J., Puig, O., Arkkila, P., Kiviluoto, T., et al. (2008). Gene expression in human NAFLD. Am J Physiol Gastrointest Liver Physiol 294:G1281–G1287
  • Guengerich, F. P. (2006). Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8:E101–E111
  • Hanagama, M., Inoue, H., Kamiya, M., Shinone, K., Nata, M. (2008). Gene expression on liver toxicity induced by administration of haloperidol in rats with severe fatty liver. Leg Med (Tokyo) 10:177–184.
  • Hardwick, R. N., Fisher, C. D., Canet, M. J., Lake, A. D., Cherrington, N. J. (2010). Diversity in antioxidant response enzymes in progressive stages of human non-alcoholic fatty liver disease. Drug Metab Dispos 38:2293–2301.
  • Harris, M. I., Cowie, C. C., Gu, K., Francis, M. E., Flegal, K., Eberhardt, M. S. (2002). Higher fasting insulin but lower fasting C-peptide levels in African Americans in the US population. Diabetes Metab Res Rev 18:149–155.
  • Hayes, J. D., Flanagan, J. U., Jowsey, I. R. (2005). Glutathione transferases. Annu Rev Pharmacol Toxicol 45:51–88.
  • Hewitt, N. J., Lechon, M. J., Houston, J. B., Hallifax, D., Brown, H. S., Maurel, P., et al. (2007). Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159–234.
  • Ipekci, S. H., Basaranoglu, M., Sonsuz, A. (2003). The fluctuation of serum levels of aminotransferase in patients with nonalcoholic steatohepatitis. J Clin Gastroenterol 36:371.
  • Ito, M., Suzuki, J., Tsujioka, S., Sasaki, M., Gomori, A., Shirakura, T., et al. (2007). Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet. Hepatol Res 37:50–57.
  • Ito, Y., Abril, E. R., Bethea, N. W., McCuskey, M. K., McCuskey, R. S. (2006). Dietary steatotic liver attenuates acetaminophen hepatotoxicity in mice. Microcirculation 13:19–27.
  • Jaiswal, A. K. (2004). Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic Biol Med 36:1199–1207.
  • Jancova, P., Anzenbacher, P., Anzenbacherova, E. (2010). Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 154:103–116.
  • Jarrar, M. H., Baranova, A., Collantes, R., Ranard, B., Stepanova, M., Bennett, C., et al. (2008). Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 27:412–421.
  • Jou, J., Choi, S. S., Diehl, A. M. (2008). Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis 28:370–379.
  • Jover, R., Moya, M., Gomez-Lechon, M. J. (2009). Transcriptional regulation of cytochrome P450 genes by the nuclear receptor hepatocyte nuclear factor 4-alpha. Curr Drug Metab 10:508–519.
  • Kader, H. H., Henderson, J., Vanhoesen, K., Ghishan, F., Bhattacharyya, A. (2008). Nonalcoholic fatty liver disease in children: a single center experience. Clin Gastroenterol Hepatol 6:799–802.
  • Kakizaki, S., Yamazaki, Y., Takizawa, D., Negishi, M. (2008). New insights on the xenobiotic-sensing nuclear receptors in liver diseases–CAR and PXR. Curr Drug Metab 9:614–621.
  • Kamiyama, Y., Matsubara, T., Yoshinari, K., Nagata, K., Kamimura, H., Yamazoe, Y. (2007). Role of human hepatocyte nuclear factor 4alpha in the Expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet 22:287–298.
  • Khemawoot, P., Yokogawa, K., Shimada, T., Miyamoto, K. (2007). Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats. Biochem Pharmacol 73:155–162.
  • Kim, M. S., Wang, S., Shen, Z., Kochansky, C. J., Strauss, J. R., Franklin, R. B., et al. (2004a). Differences in the pharmacokinetics of peroxisome proliferator-activated receptor agonists in genetically obese Zucker and Sprague-Dawley rats: implications of decreased glucuronidation in obese Zucker rats. Drug Metab Dispos 32:909–914.
  • Kim, S., Sohn, I., Ahn, J. I., Lee, K. H., Lee, Y. S., Lee, Y. S. (2004b). Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model. Gene 340:99–109.
  • Kirpich, I. A., Gobejishvili, L. N., Homme, M. B., Waigel, S., Cave, M., Arteel, G., et al. (2010). Integrated hepatic transcriptome and proteome analysis of mice with high-fat diet-induced nonalcoholic fatty liver disease. J Nutr Biochem 22:38–45.
  • Kitteringham, N. R., Abdullah, A., Walsh, J., Randle, L., Jenkins, R. E., Sison, R., et al. (2010). Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver. J Proteomics 73:1612–1631.
  • Kodama, S., Koike, C., Negishi, M., Yamamoto, Y. (2004). Nuclear receptors CAR and PXR Cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol 24:7931–7940.
  • Kohjima, M., Enjoji, M., Higuchi, N., Kato, M., Kotoh, K., Yoshimoto, T., et al. (2007). Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 20:351–358.
  • Koide, C. L., Collier, A. C., Berry, M. J., Panee, J. (2010). The effect of bamboo extract on hepatic biotransforming enzymes—findings from an obese-diabetic mouse model. J Ethnopharmacol 133:37–45.
  • Kojima, H., Sakurai, S., Matsumura, M., Umemoto, N., Uemura, M., Morimoto, H., et al. (2006). Cryptogenic cirrhosis in the region where obesity is not prevalent. World J Gastroenterol 12:2080–2085.
  • Kunde, S. S., Lazenby, A. J., Clements, R. H., Abrams, G. A. (2005). Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology 42:650–656.
  • Lamsa, V., Levonen, A. L., Leinonen, H., Yla-Herttuala, S., Yamamoto, M., Hakkola, J. (2010). Cytochrome P450 2A5 constitutive expression and induction by heavy metals is dependent on redox-sensitive transcription factor Nrf2 in liver. Chem Res Toxicol 23:977–985.
  • Larter, C. Z., Yeh, M. M. (2008). Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol 23:1635–1648.
  • Lavine, J. E., Schwimmer, J. B., Molleston, J. P., Scheimann, A. O., Murray, K. F., Abrams, S. H., et al. (2010). Treatment of nonalcoholic fatty liver disease in children: TONIC Trial Design. Contemp Clin Trials 31:62–70.
  • Lazo, M., Clark, J. M. (2008). The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis 28:339–350.
  • Leclercq, I., Horsmans, Y., Desager, J. P., Delzenne, N., Geubel, A. P. (1998). Reduction in hepatic cytochrome P-450 is correlated to the degree of liver fat content in animal models of steatosis in the absence of inflammation. J Hepatol 28:410–416.
  • Leclercq, I., Horsmans, Y., Desager, J. P., Pauwels, S., Geubel, A. P. (1999). Dietary restriction of energy and sugar results in a reduction in human cytochrome P450 2E1 activity. Br J Nutr 82:257–262.
  • Leclercq, I. A., Farrell, G. C., Field, J., Bell, D. R., Gonzalez, F. J., Robertson, G. R. (2000). CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 105:1067–1075.
  • Lee, T. Y., Chang, H. H., Lo, W. C., Lin, H. C. (2010). Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis. Int J Mol Med 25:837–844.
  • Li, P., Robertson, T. A., Thorling, C. A., Zhang, Q., Fletcher, L. M., Crawford, D. H., et al. (2011). Hepatic pharmacokinetics of cationic drugs in a high-fat emulsion-induced rat model of nonalcoholic steatohepatitis. Drug Metab Dispos 39:571–579.
  • Li, W., Kong, A. N. (2009). Molecular mechanisms of Nrf2-mediated antioxidant response. Mol Carcinog 48:91–104.
  • Lickteig, A. J. (2007). Drug metabolizing enzyme, drug transporter expression and drug disposition are altered in models of inflammatory liver disease [dissertation].
  • Lickteig, A. J., Fisher, C. D., Augustine, L. M., Cherrington, N. J. (2007). Genes of the antioxidant response undergo upregulation in a rodent model of nonalcoholic steatohepatitis. J Biochem Mol Toxicol 21:216–220.
  • Lieber, C. S., Leo, M. A., Mak, K. M., Xu, Y., Cao, Q., Ren, C., et al. (2004). Model of nonalcoholic steatohepatitis. Am J Clin Nutr 79:502–509.
  • Liston, H. L., Markowitz, J. S., DeVane, C. L. (2001). Drug glucuronidation in clinical psychopharmacology. J Clin Psychopharmacol 21:500–515.
  • Lizardi-Cervera, J., Laparra, D. I., Chavez-Tapia, N. C., Ostos, M. E., Esquivel, M. U. (2006). [Prevalence of NAFLD and metabolic syndrome in asymtomatics subjects]. Rev Gastroenterol Mex 71:453–459.
  • Lloret, L. C., Decleves, X., Oppert, J. M., Basdevant, A., Clement, K., Bardin, C., et al. (2009). Pharmacology of morphine in obese patients: clinical implications. Clin Pharmacokinet 48:635–651.
  • Loomba, R., Sirlin, C. B., Schwimmer, J. B., Lavine, J. E. (2009). Advances in pediatric nonalcoholic fatty liver disease. Hepatology 50:1282–1293.
  • Lu, S. C. (2009). Regulation of glutathione synthesis. Mol Aspects Med 30:42–59.
  • Lu, Y., Cederbaum, A. I. (2008). CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 44:723–738.
  • Ludwig, J., Viggiano, T. R., McGill, D. B., Oh, B. J. (1980). Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 55:434–438.
  • Machado, M., Marques-Vidal, P., Cortez-Pinto, H. (2006). Hepatic histology in obese patients undergoing bariatric surgery. J Hepatol 45:600–606.
  • Maclaren, N. K., Gujral, S., Ten, S., Motagheti, R. (2007). Childhood obesity and insulin resistance. Cell Biochem Biophys 48:73–78.
  • Manco, M., Putignani, L., Bottazzo, G. F. (2010). Gut microbiota, lipopolysaccharides, and innate immunity in the pathogenesis of obesity and cardiovascular risk. Endocr Rev 31:817–844.
  • Mantena, S. K., Vaughn, D. P., Andringa, K. K., Eccleston, H. B., King, A. L., Abrams, G. A., et al. (2009). High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo. Biochem J 417:183–193.
  • Marrero, J. A., Fontana, R. J., Su, G. L., Conjeevaram, H. S., Emick, D. M., Lok, A. S. (2002). NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States. Hepatology 36:1349–1354.
  • Mo, S. L., Liu, Y. H., Duan, W., Wei, M. Q., Kanwar, J. R., Zhou, S. F. (2009). Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr Drug Metab 10:730–753.
  • Mofrad, P., Contos, M. J., Haque, M., Sargeant, C., Fisher, R. A., Luketic, V. A., et al. (2003). Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 37:1286–1292.
  • Mofrad, P. S., Sanyal, A. J. (2003). Nonalcoholic fatty liver disease. MedGenMed 5:14.
  • Moran, J. R., Ghishan, F. K., Halter, S. A., Greene, H. L. (1983). Steatohepatitis in obese children: a cause of chronic liver dysfunction. Am J Gastroenterol 78:374–377.
  • Morgan, E. T. (2001). Regulation of cytochrome P450 by inflammatory mediators: why and how? Drug Metab Dispos 29:207–212.
  • Morgan, E. T. (2009). Impact of infectious and inflammatory disease on cytochrome P450-mediated drug metabolism and pharmacokinetics. Clin Pharmacol Ther 85:434–438.
  • Mottin, C. C., Moretto, M., Padoin, A. V., Swarowsky, A. M., Toneto, M. G., Glock, L., et al. (2004). The role of ultrasound in the diagnosis of hepatic steatosis in morbidly obese patients. Obes Surg 14:635–637.
  • Nakamuta, M., Kohjima, M., Morizono, S., Kotoh, K., Yoshimoto, T., Miyagi, I., et al. (2005). Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease. Int J Mol Med 16:631–635.
  • Nebert, D. W., Russell, D. W. (2002). Clinical importance of the cytochromes P450. Lancet 360:1155–1162.
  • Neuschwander-Tetri, B. A., Caldwell, S. H. (2003). Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 37:1202–1219.
  • Neyrinck, A., Eeckhoudt, S. L., Meunier, C. J., Pampfer, S., Taper, H. S., Verbeeck, R. K., et al. (1999). Modulation of paracetamol metabolism by Kupffer cells: a study on rat liver slices. Life Sci 65:2851–2859.
  • Nobili, V., Marcellini, M., Devito, R., Ciampalini, P., Piemonte, F., Comparcola, D., et al. (2006). NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 44:458–465.
  • Nowell, S., Falany, C. N. (2006). Pharmacogenetics of human cytosolic sulfotransferases. Oncogene 25:1673–1678.
  • Oh, M. K., Winn, J., Poordad, F. (2008). Review article: diagnosis and treatment of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 28:503–522.
  • Orellana, M., Rodrigo, R., Varela, N., Araya, J., Poniachik, J., Csendes, A., et al. (2006). Relationship between in vivo chlorzoxazone hydroxylation, hepatic cytochrome P450 2E1 content and liver injury in obese non-alcoholic fatty liver disease patients. Hepatol Res 34:57–63.
  • Osabe, M., Sugatani, J., Fukuyama, T., Ikushiro, S., Ikari, A., Miwa, M. (2008). Expression of hepatic UDP-glucuronosyltransferase 1A1 and 1A6 correlated with increased expression of the nuclear constitutive androstane receptor and peroxisome proliferator-activated receptor alpha in male rats fed a high-fat and high-sucrose diet. Drug Metab Dispos 36:294–302.
  • Pastore, A., Federici, G., Bertini, E., Piemonte, F. (2003). Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 333:19–39.
  • Patton, H. M., Sirlin, C., Behling, C., Middleton, M., Schwimmer, J. B., Lavine, J. E. (2006). Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research. J Pediatr Gastroenterol Nutr 43:413–427.
  • Pettinelli, P., Del, P. T., Araya, J., Rodrigo, R., Araya, A. V., Smok, G., et al. (2009). Enhancement in liver SREBP-1c/PPAR-alpha ratio and steatosis in obese patients: correlations with insulin resistance and N-3 long-chain polyunsaturated fatty acid depletion. Biochim Biophys Acta 1792:1080–1086.
  • Pi, J., Leung, L., Xue, P., Wang, W., Hou, Y., Liu, D., et al. (2010). Deficiency in the nuclear factor E2-related factor-2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity. J Biol Chem 285:9292–9300.
  • Preiss, D., Sattar, N. (2008). Non-alcoholic fatty liver disease: an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Clin Sci (Lond) 115:141–150.
  • Prompila, N., Wittayalertpanya, S., Komolmit, P. (2008). Hepatic cytochrome P450 2E1 activity in nonalcoholic fatty liver disease. J Med Assoc Thai 91:733–738.
  • Rencurel, F., Foretz, M., Kaufmann, M. R., Stroka, D., Looser, R., et al. (2006). Stimulation of AMP-activated protein kinase is essential for the induction of drug metabolizing enzymes by phenobarbital in human and mouse liver. Mol Pharmacol 70:1925–1934.
  • Rencurel, F., Stenhouse, A., Hawley, S. A., Friedberg, T., Hardie, D. G., Sutherland, C., et al. (2005). AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. J Biol Chem 280:4367–4373.
  • Reynaert, H., Geerts, A., Henrion, J. (2005). Review article: the treatment of non-alcoholic steatohepatitis with thiazolidinediones. Aliment Pharmacol Ther 22:897–905.
  • Roberts, E. A. (2007). Pediatric nonalcoholic fatty liver disease (NAFLD): a “growing” problem? J Hepatol 46:1133–1142.
  • Roe, A. L., Howard, G., Blouin, R., Snawder, J. E. (1999). Characterization of cytochrome P450 and glutathione S-transferase activity and expression in male and female ob/ob mice. Int J Obes Relat Metab Disord 23:48–53.
  • Roth, A., Looser, R., Kaufmann, M., Blattler, S. M., Rencurel, F., Huang, W., et al. (2008a). Regulatory cross-talk between drug metabolism and lipid homeostasis: constitutive androstane receptor and pregnane X receptor increase Insig-1 expression. Mol Pharmacol 73:1282–1289.
  • Roth, A., Looser, R., Kaufmann, M., Meyer, U. A. (2008b). Sterol regulatory element binding protein 1 interacts with pregnane X receptor and constitutive androstane receptor and represses their target genes. Pharmacogenet Genomics 18:325–337.
  • Rubio, A., Guruceaga, E., Vazquez-Chantada, M., Sandoval, J., Martinez-Cruz, L. A., Segura, V., et al. (2007). Identification of a gene-pathway associated with non-alcoholic steatohepatitis. J Hepatol 46:708–718.
  • Schwimmer, J. B., Deutsch, R., Kahen, T., Lavine, J. E., Stanley, C., Behling, C. (2006). Prevalence of fatty liver in children and adolescents. Pediatrics 118:1388–1393.
  • Schwimmer, J. B., McGreal, N., Deutsch, R., Finegold, M. J., Lavine, J. E. (2005). Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents. Pediatrics 115:e561–e565
  • Sharma, A., Bartell, S. M., Baile, C. A., Chen, B., Podolsky, R. H., McIndoe, R. A., et al. (2010). Hepatic gene expression profiling reveals key pathways involved in leptin-mediated weight loss in ob/ob mice. PLoS One 5:e12147.
  • Shedlofsky, S. I., Israel, B. C., McClain, C. J., Hill, D. B., Blouin, R. A. (1994). Endotoxin administration to humans inhibits hepatic cytochrome P450-mediated drug metabolism. J Clin Invest 94:2209–2214.
  • Shen, G., Kong, A. N. (2009). Nrf2 plays an important role in coordinated regulation of phase II drug metabolism enzymes and phase III drug transporters. Biopharm Drug Dispos 30:345–355.
  • Shin, S., Wakabayashi, J., Yates, M. S., Wakabayashi, N., Dolan, P. M., Aja, S., et al. (2009). Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur J Pharmacol 620:138–144.
  • Shindo, S., Numazawa, S., Yoshida, T. (2007). A physiological role of AMP-activated protein kinase in phenobarbital-mediated constitutive androstane receptor activation and CYP2B induction. Biochem J 401:735–741.
  • Skouby, S. O. (2010). Hormonal contraception in obesity, the metabolic syndrome, and diabetes. Ann N Y Acad Sci 1205:240–244.
  • Sorrentino, P., Tarantino, G., Conca, P., Perrella, A., Terracciano, M. L., Vecchione, R., et al. (2004). Silent non-alcoholic fatty liver disease—a clinical-histological study. J Hepatol 41:751–757.
  • Stepanova, M., Hossain, N., Afendy, A., Perry, K., Goodman, Z. D., Baranova, A., et al. (2010). Hepatic gene expression of Caucasian and African-American patients with obesity-related non-alcoholic fatty liver disease. Obes Surg 20:640–650.
  • Sugatani, J., Wada, T., Osabe, M., Yamakawa, K., Yoshinari, K., Miwa, M. (2006). Dietary insulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab Dispos 34:1677–1687.
  • Sugimoto, H., Okada, K., Shoda, J., Warabi, E., Ishige, K., Ueda, T., et al. (2010). Deletion of nuclear factor-E2-related factor-2 leads to rapid onset and progression of nutritional steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol 298:G283–G294
  • Suh, Y. H., Kim, Y., Bang, J. H., Choi, K. S., Lee, J. W., Kim, W. H., et al. (2005). Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats. J Mol Endocrinol 34:299–315.
  • Tanaka, E., Terada, M., Misawa, S. (2000). Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther 25:165–175.
  • Tanaka, N., Ichijo, T., Okiyama, W., Mutou, H., Misawa, N., Matsumoto, A., et al. (2006). Laparoscopic findings in patients with nonalcoholic steatohepatitis. Liver Int 26:32–38.
  • Tarantino, G., Conca, P., Basile, V., Gentile, A., Capone, D., Polichetti, G., et al. (2007). A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res 37:410–415.
  • Tarantino, G., Di Minno, M. N., Capone, D. (2009). Drug-induced liver injury: is it somehow foreseeable? World J Gastroenterol 15:2817–2833.
  • Thampanitchawong, P., Piratvisuth, T. (1999). Liver biopsy: complications and risk factors. World J Gastroenterol 5:301–304.
  • Tiniakos, D. G., Vos, M. B., Brunt, E. M. (2010). Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 5:145–171.
  • Uslusoy, H. S., Nak, S. G., Gulten, M., Biyikli, Z. (2009). Non-alcoholic steatohepatitis with normal aminotransferase values. World J Gastroenterol 15:1863–1868.
  • Videla, L. A., Rodrigo, R., Orellana, M., Fernandez, V., Tapia, G., Quinones, L., et al. (2004). Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci (Lond) 106:261–268.
  • Wang, B., Yang, L. P., Zhang, X. Z., Huang, S. Q., Bartlam, M., Zhou, S. F. (2009). New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme. Drug Metab Rev 41:573–643.
  • Wang, Y., Beydoun, M. A., Liang, L., Caballero, B., Kumanyika, S. K. (2008). Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring) 16:2323–2330.
  • Watson, A. M., Poloyac, S. M., Howard, G., Blouin, R. A. (1999). Effect of leptin on cytochrome P-450, conjugation, and antioxidant enzymes in the ob/ob mouse. Drug Metab Dispos 27:695–700.
  • Weltman, M. D., Farrell, G. C., Hall, P., Ingelman-Sundberg, M., Liddle, C. (1998). Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 27:128–133.
  • Weltman, M. D., Farrell, G. C., Liddle, C. (1996). Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology 111:1645–1653.
  • Wieckowska, A., Feldstein, A. E. (2008). Diagnosis of nonalcoholic fatty liver disease: invasive versus noninvasive. Semin Liver Dis 28:386–395.
  • Wieckowska, A., Papouchado, B. G., Li, Z., Lopez, R., Zein, N. N., Feldstein, A. E. (2008). Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 103:1372–1379.
  • Williams, J. A., Hyland, R., Jones, B. C., Smith, D. A., Hurst, S., Goosen, T. C., et al. (2004). Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201–1208.
  • Yamazaki, Y., Kakizaki, S., Horiguchi, N., Sohara, N., Sato, K., Takagi, H., et al. (2007). The role of the nuclear receptor constitutive androstane receptor in the pathogenesis of non-alcoholic steatohepatitis. Gut 56:565–574.
  • Yoneda, M, Endo, H, Mawatari, H, Nozaki, Y, Fujita, K, Akiyama, T, et al. (2008). Gene expression profiling of non-alcoholic steatohepatitis using gene set enrichment analysis. Hepatol Res 38:1204–1212.
  • Yoshinari, K., Takagi, S., Sugatani, J., Miwa, M. (2006). Changes in the expression of cytochromes P450 and nuclear receptors in the liver of genetically diabetic db/db mice. Biol Pharm Bull 29:1634–1638.
  • Younossi, Z. M., Baranova, A., Ziegler, K., Del, G. L., Schlauch, K., Born, T. L., et al. (2005a). A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease. Hepatology 42:665–674.
  • Younossi, Z. M., Gorreta, F., Ong, J. P., Schlauch, K., Del, G. L., Elariny, H., et al. (2005b). Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis. Liver Int 25:760–771.
  • Zanger, U. M., Klein, K., Richter, T., Toscano, C., Zukunft, J. (2005). Impact of Genetic Polymorphism in relation to other factors on expression and function of human drug-metabolizing P450s. Toxicol Mech Meth 15:121–124.
  • Zhai, Y., Wada, T., Zhang, B., Khadem, S., Ren, S., Kuruba, R., et al. (2010). A functional cross-talk between liver X receptor-alpha and constitutive androstane receptor links lipogenesis and xenobiotic responses. Mol Pharmacol 78:666–674.
  • Zhang, D. D. (2006). Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev 38:769–789.
  • Zhang, W. V., Ramzan, I., Murray, M. (2007). Impaired microsomal oxidation of the atypical antipsychotic agent clozapine in hepatic steatosis. J Pharmacol Exp Ther 322:770–777.
  • Zhang, Y. K., Yeager, R. L., Tanaka, Y., Klaassen, C. D. (2010). Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet. Toxicol Appl Pharmacol 245:326–334.
  • Zhou, S. F. (2008). Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9:310–322.
  • Zhou, S. F., Chan, E., Zhou, Z. W., Xue, C. C., Lai, X., Duan, W. (2009). Insights into the structure, function, and regulation of human cytochrome P450 1A2. Curr Drug Metab 10:713–729.

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