Role of the constitutive androstane receptor in obesity and type 2 diabetes: a case study of the endobiotic function of a xenobiotic receptor

References

• Aleksunes, L. M., Klaassen, C. D. (2012). Coordinated regulation of hepatic phase I and II drug-metabolizing genes and transporters using AhR-, CAR-, PXR-, PPARalpha-, and Nrf2-null mice. Drug Metab Dispos 40:1366–1379.
   PubMed Web of Science ®Google Scholar
• Alnouti, Y., Klaassen, C. D. (2008). Regulation of sulfotransferase enzymes by prototypical microsomal enzyme inducers in mice. J Pharmacol Exp Ther 324:612–621.
   PubMed Web of Science ®Google Scholar
• Argaud, D., Halimi, S., Catelloni, F., Leverve, X. M. (1991). Inhibition of gluconeogenesis in isolated rat hepatocytes after chronic treatment with phenobarbital. Biochem J 280:663–669.
   PubMed Web of Science ®Google Scholar
• Baes, M., Gulick, T., Choi, H. S., Martinoli, M. G., Simha, D., Moore, D. D. (1994). A new orphan member of the nuclear hormone receptor superfamily that interacts with a subset of retinoic acid response elements. Mol Cell Biol 14:1544–1552.
   PubMed Web of Science ®Google Scholar
• Bai, Q., Zhang, X., Xu, L., Kakiyama, G., Heuman, D., Sanyal, A., et al. (2012). Oxysterol sulfation by cytosolic sulfotransferase suppresses liver X receptor/sterol regulatory element binding protein-1c signaling pathway and reduces serum and hepatic lipids in mouse models of nonalcoholic fatty liver disease. Metabolism 61:836–845.
   PubMed Web of Science ®Google Scholar
• Benhamed, F., Denechaud, P. D., Lemoine, M., Robichon, C., Moldes, M., Bertrand-Michel, J., et al. (2012). The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans. J Clin Invest 122:2176–2194.
   PubMed Web of Science ®Google Scholar
• Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., et al. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857–868.
   PubMed Web of Science ®Google Scholar
• Brunton, L. L., Knollmann, B. A. C. (2011). Goodman & Gilman’s the pharmacological basis of therapeutics, 12th edition. New York: McGraw-Hill.
   Google Scholar
• Burgess, S. C., He, T., Yan, Z., Lindner, J., Sherry, A. D., Malloy, C. R., et al. (2007). Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab 5:313–320.
   PubMed Web of Science ®Google Scholar
• Chakraborty, S., Kanakasabai, S., Bright, J. J. (2011). Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells. Br J Cancer 104: 448–459.
   PubMed Web of Science ®Google Scholar
• Chen, W., Chen, G., Head, D. L., Mangelsdorf, D. J., Russell, D. W. (2007). Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice. Cell Metab 5:73–79.
   PubMed Web of Science ®Google Scholar
• Chen, W. D., Fu, X., Dong, B., Wang, Y. D., Shiah, S., Moore, D. D., et al. (2012). Neonatal activation of the nuclear receptor CAR results in epigenetic memory and permanent change of drug metabolism in mouse liver. Hepatology 56:1499–1508.
   PubMed Web of Science ®Google Scholar
• Clemmesen, J., Hjalgrim-Jensen, S. (1978). Is phenobarbital carcinogenic? A follow-up of 8078 epileptics. Ecotoxicol Environ Saf 1:457–470.
   PubMed Web of Science ®Google Scholar
• Ding, X., Lichti, K., Kim, I., Gonzalez, F. J., Staudinger, J. L. (2006). Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha. J Biol Chem 281:26540–26551.
   PubMed Web of Science ®Google Scholar
• Dong, B., Qatanani, M., Moore, D. D. (2009a). Constitutive androstane receptor mediates the induction of drug metabolism in mouse models of type 1 diabetes. Hepatology 50:622–629.
   PubMed Web of Science ®Google Scholar
• Dong, B., Saha, P. K., Huang, W., Chen, W., Abu-Elheiga, L. A., Wakil, S. J., et al. (2009b). Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease. Proc Natl Acad Sci U S A 106:18831–18836.
   PubMed Web of Science ®Google Scholar
• Drake, A. J., Reynolds, R. M. (2010). Impact of maternal obesity on offspring obesity and cardiometabolic disease risk. Reproduction 140:387–398.
   PubMed Web of Science ®Google Scholar
• Duckitt, K., Harrington, D. (2005). Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 330:565.
   PubMed Web of Science ®Google Scholar
• Foretz, M., Hebrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., et al. (2010). Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 120:2355–2369.
   PubMed Web of Science ®Google Scholar
• Forman, B. M., Tzameli, I., Choi, H. S., Chen, J., Simha, D., Seol, W., et al. (1998). Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta. Nature 395:612–615.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Grundy, S. M. (2004). Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 89:2595–2600.
   PubMed Web of Science ®Google Scholar
• Hollander, M. H., Paarlberg, K. M., Huisjes, A. J. (2007). Gestational diabetes: a review of the current literature and guidelines. Obstet Gynecol Surv 62:125–136.
   PubMed Web of Science ®Google Scholar
• Honkakoski, P., Zelko, I., Sueyoshi, T., Negishi, M. (1998). The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene. Mol Cell Biol 18:5652–5658.
   PubMed Web of Science ®Google Scholar
• Horton, J. D., Goldstein, J. L., Brown, M. S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 109:1125–1131.
   PubMed Web of Science ®Google Scholar
• Hosseinpour, F., Moore, R., Negishi, M., Sueyoshi, T. (2006). Serine 202 regulates the nuclear translocation of constitutive active/androstane receptor. Mol Pharmacol 69:1095–1102.
   PubMed Web of Science ®Google Scholar
• Huang, W., Zhang, J., Washington, M., Liu, J., Parant, J. M., Lozano, G., et al. (2005). Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol Endocrinol 19:1646–1653.
   PubMed Web of Science ®Google Scholar
• Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V., Chandramouli, V., et al. (2000). Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 49:2063–2069.
   PubMed Web of Science ®Google Scholar
• Kachaylo, E. M., Pustylnyak, V. O., Lyakhovich, V. V., Gulyaeva, L. F. (2011). Constitutive androstane receptor (CAR) is a xenosensor and target for therapy. Biochemistry (Mosc) 76:1087–1097.
   PubMed Web of Science ®Google Scholar
• Karvonen, I., Stengard, J. H., Huupponen, R., Stenback, F. G., Sotaniemi, E. A. (1989). Effects of enzyme induction therapy on glucose and drug metabolism in obese mice model of non-insulin dependent diabetes mellitus. Diabetes Res 10:85–92.
   PubMedGoogle Scholar
• Kawamoto, T., Sueyoshi, T., Zelko, I., Moore, R., Washburn, K., Negishi, M. (1999). Phenobarbital-responsive nuclear translocation of the receptor CAR in induction of the CYP2B gene. Mol Cell Biol 19:6318–6322.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Konno, Y., Negishi, M., Kodama, S. (2008). The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab Pharmacokinet 23:8–13.
   PubMed Web of Science ®Google Scholar
• Lahtela, J. T., Arranto, A. J., Sotaniemi, E. A. (1985). Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects. Diabetes 34:911–916.
   PubMed Web of Science ®Google Scholar
• 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. Proc Natl Acad Sci U S A 107:3441–3446.
   PubMed Web of Science ®Google Scholar
• Ma, Y., Xu, L., Rodriguez-Agudo, D., Li, X., Heuman, D. M., Hylemon, P. B., et al. (2008). 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am J Physiol Endocrinol Metab 295:E1369–E1379.
   PubMed Web of Science ®Google Scholar
• Maglich, J. M., Parks, D. J., Moore, L. B., Collins, J. L., Goodwin, B., Billin, A. N., et al. (2003). Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J Biol Chem 278:17277–17283.
   PubMed Web of Science ®Google Scholar
• Maglich, J. M., Watson, J., McMillen, P. J., Goodwin, B., Willson, T. M., Moore, J. T. (2004). The nuclear receptor CAR is a regulator of thyroid hormone metabolism during caloric restriction. J Biol Chem 279:19832–19838.
   PubMed Web of Science ®Google Scholar
• Magnusson, I., Rothman, D. L., Katz, L. D., Shulman, R. G., Shulman, G. I. (1992). Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest 90:1323–1327.
   PubMed Web of Science ®Google Scholar
• Masuyama, H., Hiramatsu, Y. (2011). Potential role of estradiol and progesterone in insulin resistance through constitutive androstane receptor. J Mol Endocrinol 47:229–239.
   PubMed Web of Science ®Google Scholar
• Masuyama, H., Hiramatsu, Y. (2012a). Treatment with a constitutive androstane receptor ligand ameliorates the signs of preeclampsia in high-fat diet-induced obese pregnant mice. Mol Cell Endocrinol 348:120–127.
   PubMed Web of Science ®Google Scholar
• Masuyama, H., Hiramatsu, Y. (2012b). Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice. Am J Physiol Endocrinol Metab 303:E293–E300.
   PubMed Web of Science ®Google Scholar
• Miao, J., Fang, S., Bae, Y., Kemper, J. K. (2006). Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1alpha. J Biol Chem 281:14537–14546.
   PubMed Web of Science ®Google Scholar
• Min, G., Kim, H., Bae, Y., Petz, L., Kemper, J. K. (2002). Inhibitory cross-talk between estrogen receptor (ER) and constitutively activated androstane receptor (CAR). CAR inhibits ER-mediated signaling pathway by squelching p160 coactivators. J Biol Chem 277:34626–34633.
   PubMed Web of Science ®Google Scholar
• Monetti, M., Levin, M. C., Watt, M. J., Sajan, M. P., Marmor, S., Hubbard, B. K., et al. (2007). Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab 6:69–78.
   PubMed Web of Science ®Google Scholar
• Moore, D. D. (2012). Nuclear receptors reverse McGarry’s vicious cycle to insulin resistance. Cell Metab 15:615–622.
   PubMed Web of Science ®Google Scholar
• Nakae, J., Kitamura, T., Silver, D. L., Accili, D. (2001). The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108:1359–1367.
   PubMed Web of Science ®Google Scholar
• Ooe, H., Kon, J., Oshima, H., Mitaka, T. (2009). Thyroid hormone is necessary for expression of constitutive androstane receptor in rat hepatocytes. Drug Metab Dispos 37:1963–1969.
   PubMed Web of Science ®Google Scholar
• Park, Y. J., Lee, E. K., Lee, Y. K., Park do, J., Jang, H. C., Moore, D. D. (2012). Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice. Toxicol Appl Pharmacol 263:131–137.
   PubMed Web of Science ®Google Scholar
• Qatanani, M., Zhang, J., Moore, D. D. (2005). Role of the constitutive androstane receptor in xenobiotic-induced thyroid hormone metabolism. Endocrinology 146:995–1002.
   PubMed Web of Science ®Google Scholar
• Rawson, R. B. (2003). The SREBP pathway—insights from Insigs and insects. Nat Rev Mol Cell Biol 4:631–640.
   PubMed Web of Science ®Google Scholar
• Rencurel, F., Foretz, M., Kaufmann, M. R., Stroka, D., Looser, R., Leclerc, I., 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.
   PubMed Web of Science ®Google Scholar
• Ross, J., Plummer, S. M., Rode, A., Scheer, N., Bower, C. C., Vogel, O., et al. (2010). Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol Sci 116:452–466.
   PubMed Web of Science ®Google Scholar
• Roth, A., Looser, R., Kaufmann, M., Blattler, S. M., Rencurel, F., Huang, W., et al. (2008). 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.
   PubMed Web of Science ®Google Scholar
• Shiraki, T., Sakai, N., Kanaya, E., Jingami, H. (2003). Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha. A possible link between xenobiotic response and nutritional state. J Biol Chem 278:11344–11350.
   PubMed Web of Science ®Google Scholar
• Shizu, R., Shindo, S., Yoshida, T., Numazawa, S. (2012). MicroRNA-122 down-regulation is involved in phenobarbital-mediated activation of the constitutive androstane receptor. PLoS One 7:e41291.
   PubMed Web of Science ®Google Scholar
• Song, W. C. (2001). Biochemistry and reproductive endocrinology of estrogen sulfotransferase. Ann N Y Acad Sci 948:43–50.
   PubMed Web of Science ®Google Scholar
• Sotaniemi, E. A., Karvonen, I. (1989). Glucose tolerance and insulin response to glucose load before and after enzyme inducing therapy in subjects with glucose intolerance and patients with NIDDM having hyperinsulinemia or relative insulin deficiency. Diabetes Res 11:131–139.
   PubMedGoogle Scholar
• Stengard, J. H., Saarni, H. U., Karvonen, R. I., Lahtela, J. T., Karki, N. T., Stenback, F., et al. (1987). Hepatic drug metabolism and the activities of NADPH generating enzymes and glucose-6-phosphatase in phenobarbital treated genetically obese (ob/ob) mice. Biomed Pharmacother 41:389–396.
   PubMed Web of Science ®Google Scholar
• Sueyoshi, T., Green, W. D., Vinal, K., Woodrum, T. S., Moore, R., Negishi, M. (2011). Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver. PLoS One 6:e21229.
   PubMed Web of Science ®Google Scholar
• Sun, Y., Liu, S., Ferguson, S., Wang, L., Klepcyk, P., Yun, J. S., et al. (2002). Phosphoenolpyruvate carboxykinase overexpression selectively attenuates insulin signaling and hepatic insulin sensitivity in transgenic mice. J Biol Chem 277:23301–23307.
   PubMed Web of Science ®Google Scholar
• Tajima, M., Ikarashi, N., Imahori, Y., Okaniwa, T., Saruta, K., Ishii, M., et al. (2012). Consumption of a high-fat diet during pregnancy decreases the activity of cytochrome P450 3a in the livers of offspring. Eur J Pharm Sci 47:108–116.
   PubMed Web of Science ®Google Scholar
• Thurman, R.G., Marazzo, D. P. (1975). Mixed function oxidation and intermediary metabolism: metabolic interdependencies in the liver. Adv Exp Med Biol 58:355–367.
   PubMedGoogle Scholar
• Timsit, Y. E., Negishi, M. (2007). CAR and PXR: the xenobiotic-sensing receptors. Steroids 72:231–246.
   PubMed Web of Science ®Google Scholar
• Tzameli, I., Pissios, P., Schuetz, E. G., Moore, D. D. (2000). The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol Cell Biol 20:2951–2958.
   PubMed Web of Science ®Google Scholar
• Ueda, A., Hamadeh, H. K., Webb, H. K., Yamamoto, Y., Sueyoshi, T., Afshari, C. A., et al. (2002a). Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 61:1–6.
   PubMed Web of Science ®Google Scholar
• Ueda, A., Hamadeh, H. K., Webb, H. K., Yamamoto, Y., Sueyoshi, T., Afshari, C. A., et al. (2002b). Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital. Mol Pharmacol 61:1–6.
   PubMed Web of Science ®Google Scholar
• Valera, A., Pujol, A., Pelegrin, M., Bosch, F. (1994). Transgenic mice overexpressing phosphoenolpyruvate carboxykinase develop non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 91:9151–9154.
   PubMed Web of Science ®Google Scholar
• Venkatesan, N., Davidson, M. B., Simsolo, R. B., Kern, P.A. (1994). Phenobarbital treatment enhances insulin-mediated glucose metabolism and improves lipid metabolism in the diabetic rat. Metabolism 43:348–356.
   PubMed Web of Science ®Google Scholar
• Xie, W., Uppal, H., Saini, S. P., Mu, Y., Little, J. M., Radominska-Pandya, A., et al. (2004). Orphan nuclear receptor-mediated xenobiotic regulation in drug metabolism. Drug Discov Today 9:442–449.
   PubMed Web of Science ®Google Scholar
• Xu, L., Bai, Q., Rodriguez-Agudo, D., Hylemon, P. B., Heuman, D. M., Pandak, W. M., et al. (2010). Regulation of hepatocyte lipid metabolism and inflammatory response by 25-hydroxycholesterol and 25-hydroxycholesterol-3-sulfate. Lipids 45:821–832.
   PubMed Web of Science ®Google Scholar
• Yamamoto, Y., Moore, R., Goldsworthy, T. L., Negishi, M., Maronpot, R. R. (2004). The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res 64:7197–7200.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Zhang, J., Huang, W., Chua, S. S., Wei, P., Moore, D. D. (2002). Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 298:422–424.
   PubMed Web of Science ®Google Scholar
• Zimmet, P., Alberti, K. G., Shaw, J. (2001). Global and societal implications of the diabetes epidemic. Nature 414:782–787.
   PubMed Web of Science ®Google Scholar