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Review Article

CB1拮抗对非酒精性脂肪性肝病肝脏氧化/亚硝化应激和炎症的影响

卷 28, 期 1, 2021

发表于: 03 March, 2020

页: [169 - 180] 页: 12

弟呕挨: 10.2174/0929867327666200303122734

价格: $65

摘要

内源性大麻素系统(ES)功能障碍已在非酒精性脂肪性肝病(NAFLD)和相关的代谢紊乱中被确认。大麻素受体1型(CB1)的表达在很大程度上取决于营养状况。因此，NAFLD和代谢综合征(MS)患者的ES活性显著增加。此外，肝脏的氧化/亚硝化应激和炎症过程调节高度受ES影响。大量实验研究表明，肝脏的氧化和亚硝化应激与NAFLD期间的脂肪变性和门脉炎症有关。另一方面，炎症本身也可能由于枯否细胞的活化和烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性的增加而促进活性氧(ROS)的产生。内源性大麻素及其脂质相关介质调节氧化应激和脂质过氧化的途径是一个重要的研究领域，可以为NAFLD的治疗提供新的药物策略。累积的证据表明ES，特别是CB1受体，可能也在炎症和疾病进展到脂肪性肝炎中发挥作用。NAFLD中CB1受体的药理失活具有多种有益作用，特别是由于肝脏氧化/亚硝化应激参数的衰减和促炎细胞因子的显著减少。然而，在进入临床研究阶段之前，需要对CB1封锁影响肝脏氧化/亚硝化应激和炎症减少的确切机制进行进一步的研究。

关键词: NAFLD，内源性大麻素，CB受体，CB1拮抗，氧化/亚硝化应激，炎症，内源性大麻素系统(ES)。

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[1]
Kuipers, E.N.; Kantae, V.; Maarse, B.C.E.; van den Berg, S.M.; van Eenige, R.; Nahon, K.J.; Reifel-Miller, A.; Coskun, T.; de Winther, M.P.J.; Lutgens, E.; Kooijman, S.; Harms, A.C.; Hankemeier, T.; van der Stelt, M.; Rensen, P.C.N.; Boon, M.R. High fat diet increases circulating endocannabinoids accompanied by increased synthesis enzymes in adipose tissue. Front. Physiol., 2019, 9, 1913.
[http://dx.doi.org/10.3389/fphys.2018.01913] [PMID: 30687125]
[2]
Shrestha, N.; Cuffe, J.S.M.; Hutchinson, D.S.; Headrick, J.P.; Perkins, A.V.; McAinch, A.J.; Hryciw, D.H. Peripheral modulation of the endocannabinoid system in metabolic disease. Drug Discov. Today, 2018, 23(3), 592-604.
[http://dx.doi.org/10.1016/j.drudis.2018.01.029] [PMID: 29331500]
[3]
Kim, D.; Kim, W.; Kwak, M.S.; Chung, G.E.; Yim, J.Y.; Ahmed, A. Inverse association of marijuana use with nonalcoholic fatty liver disease among adults in the United States. PLoS One, 2017, 12(10)e0186702
[http://dx.doi.org/10.1371/journal.pone.0186702] [PMID: 29049354]
[4]
Alswat, K.A. The role of endocannabinoids system in fatty liver disease and therapeutic potentials. Saudi J. Gastroenterol., 2013, 19(4), 144-151.
[http://dx.doi.org/10.4103/1319-3767.114505] [PMID: 23828743]
[5]
Di Marzo, V. CB(1) receptor antagonism: biological basis for metabolic effects. Drug Discov. Today, 2008, 13(23-24), 1026-1041.
[http://dx.doi.org/10.1016/j.drudis.2008.09.001] [PMID: 18824122]
[6]
Huffman, J.W.; Yu, S.; Showalter, V.; Abood, M.E.; Wiley, J.L.; Compton, D.R.; Martin, B.R.; Bramblett, R.D.; Reggio, P.H. Synthesis and pharmacology of a very potent cannabinoid lacking a phenolic hydroxyl with high affinity for the CB2 receptor. J. Med. Chem., 1996, 39(20), 3875-3877.
[http://dx.doi.org/10.1021/jm960394y] [PMID: 8831752]
[7]
Svízenská, I.; Dubový, P.; Sulcová, A. Cannabinoid receptors 1 and 2 (CB1 and CB2), their distribution, ligands and functional involvement in nervous system structures--a short review. Pharmacol. Biochem. Behav., 2008, 90(4), 501-511.
[http://dx.doi.org/10.1016/j.pbb.2008.05.010] [PMID: 18584858]
[8]
Pertwee, R.G. The pharmacology of cannabinoid receptors and their ligands: an overview. Int. J. Obes., 2006, 30(Suppl. 1), S13-S18.
[http://dx.doi.org/10.1038/sj.ijo.0803272] [PMID: 16570099]
[9]
Bermudez-Silva, F.J.; Viveros, M.P.; McPartland, J.M.; Rodriguez de Fonseca, F. The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacol. Biochem. Behav., 2010, 95(4), 375-382.
[http://dx.doi.org/10.1016/j.pbb.2010.03.012] [PMID: 20347862]
[10]
Silvestri, C.; Di Marzo, V. The endocannabinoid system in energy homeostasis and the etiopathology of metabolic disorders. Cell Metab., 2013, 17(4), 475-490.
[http://dx.doi.org/10.1016/j.cmet.2013.03.001] [PMID: 23562074]
[11]
Matias, I.; Gonthier, M.P.; Orlando, P.; Martiadis, V.; De Petrocellis, L.; Cervino, C.; Petrosino, S.; Hoareau, L.; Festy, F.; Pasquali, R.; Roche, R.; Maj, M.; Pagotto, U.; Monteleone, P.; Di Marzo, V. Regulation, function, and dysregulation of endocannabinoids in models of adipose and β-pancreatic cells and in obesity and hyperglycemia. J. Clin. Endocrinol. Metab., 2006, 91(8), 3171-3180.
[http://dx.doi.org/10.1210/jc.2005-2679] [PMID: 16684820]
[12]
Di Marzo, V.; De Petrocellis, L. Endocannabinoids as regulators of transient receptor potential (TRP) channels: A further opportunity to develop new endocannabinoid-based therapeutic drugs. Curr. Med. Chem., 2010, 17(14), 1430-1449.
[http://dx.doi.org/10.2174/092986710790980078] [PMID: 20166923]
[13]
Pertwee, R.G. Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications. Proc. Nutr. Soc., 2014, 73(1), 96-105.
[http://dx.doi.org/10.1017/S0029665113003649] [PMID: 24135210]
[14]
Laprairie, R.B.; Bagher, A.M.; Kelly, M.E.; Denovan-Wright, E.M. Biased type 1 cannabinoid receptor signaling influences neuronal viability in a cell culture model of Huntington disease. Mol. Pharmacol., 2016, 89(3), 364-375.
[http://dx.doi.org/10.1124/mol.115.101980] [PMID: 26700564]
[15]
Soethoudt, M.; Grether, U.; Fingerle, J.; Grim, T.W.; Fezza, F.; de Petrocellis, L.; Ullmer, C.; Rothenhäusler, B.; Perret, C.; van Gils, N.; Finlay, D.; MacDonald, C.; Chicca, A.; Gens, M.D.; Stuart, J.; de Vries, H.; Mastrangelo, N.; Xia, L.; Alachouzos, G.; Baggelaar, M.P.; Martella, A.; Mock, E.D.; Deng, H.; Heitman, L.H.; Connor, M.; Di Marzo, V.; Gertsch, J.; Lichtman, A.H.; Maccarrone, M.; Pacher, P.; Glass, M.; van der Stelt, M. Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity. Nat. Commun., 2017, 8, 13958.
[http://dx.doi.org/10.1038/ncomms13958] [PMID: 28045021]
[16]
Hudson, B.D.; Hébert, T.E.; Kelly, M.E.M. Ligand- and heterodimer-directed signaling of the CB(1) cannabinoid receptor. Mol. Pharmacol., 2010, 77(1), 1-9.
[http://dx.doi.org/10.1124/mol.109.060251] [PMID: 19837905]
[17]
Jorgačević, B.; Mladenović, D.; Ninković, M.; Vesković, M.; Dragutinović, V.; Vatazević, A.; Vučević, D.; Ješić Vukićević, R.; Radosavljević, T. Rimonabant improves oxidative/nitrosative stress in mice with nonalcoholic fatty liver disease. Oxid. Med. Cell. Longev., 2015, 2015842108
[http://dx.doi.org/10.1155/2015/842108] [PMID: 26078820]
[18]
Jorgačević, B.; Vučević, D.; Đuričić, I.; Šobajić, S.; Mladenović, D.; Vesković, M.; Vukićević, R.J.; Radosavljević, T. The effect of cannabinoid receptor 1 blockade on hepatic free fatty acid profile in mice with nonalcoholic fatty liver disease. Chem. Phys. Lipids, 2017, 204, 85-93.
[http://dx.doi.org/10.1016/j.chemphyslip.2017.03.009] [PMID: 28363784]
[19]
Jorgačević, B.; Vučević, D.; Vesković, M.; Mladenović, D.; Vukićević, D.; Vukićević, R.J.; Todorović, V.; Radosavljević, T. The effect of cannabinoid receptor 1 blockade on adipokine and proinflammatory cytokine concentration in adipose and hepatic tissue in mice with nonalcoholic fatty liver disease. Can. J. Physiol. Pharmacol., 2019, 97(2), 120-129.
[http://dx.doi.org/10.1139/cjpp-2018-0607] [PMID: 30673308]
[20]
Jeong, W.I.; Osei-Hyiaman, D.; Park, O.; Liu, J.; Bátkai, S.; Mukhopadhyay, P.; Horiguchi, N.; Harvey-White, J.; Marsicano, G.; Lutz, B.; Gao, B.; Kunos, G. Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab., 2008, 7(3), 227-235.
[http://dx.doi.org/10.1016/j.cmet.2007.12.007] [PMID: 18316028]
[21]
Mukhopadhyay, B.; Liu, J.; Osei-Hyiaman, D.; Godlewski, G.; Mukhopadhyay, P.; Wang, L.; Jeong, W.I.; Gao, B.; Duester, G.; Mackie, K.; Kojima, S.; Kunos, G. Transcriptional regulation of cannabinoid receptor-1 expression in the liver by retinoic acid acting via retinoic acid receptor-gamma. J. Biol. Chem., 2010, 285(25), 19002-19011.
[http://dx.doi.org/10.1074/jbc.M109.068460] [PMID: 20410309]
[22]
Zelber-Sagi, S.; Azar, S.; Nemirovski, A.; Webb, M.; Halpern, Z.; Shibolet, O.; Tam, J. Serum levels of endocannabinoids are independently associated with nonalcoholic fatty liver disease. Obesity (Silver Spring), 2017, 25(1), 94-101.
[http://dx.doi.org/10.1002/oby.21687] [PMID: 27863097]
[23]
Rolo, A.P.; Teodoro, J.S.; Palmeira, C.M. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic. Biol. Med., 2012, 52(1), 59-69.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.003] [PMID: 22064361]
[24]
Gornicka, A.; Morris-Stiff, G.; Thapaliya, S.; Papouchado, B.G.; Berk, M.; Feldstein, A.E. Transcriptional profile of genes involved in oxidative stress and antioxidant defense in a dietary murine model of steatohepatitis. Antioxid. Redox Signal., 2011, 15(2), 437-445.
[http://dx.doi.org/10.1089/ars.2010.3815] [PMID: 21194384]
[25]
Sureshbabu, A.; Ryter, S.W.; Choi, M.E. Oxidative stress and autophagy: crucial modulators of kidney injury. Redox Biol., 2015, 4, 208-214.
[http://dx.doi.org/10.1016/j.redox.2015.01.001] [PMID: 25613291]
[26]
Mukhopadhyay, P.; Pan, H.; Rajesh, M.; Bátkai, S.; Patel, V.; Harvey-White, J.; Mukhopadhyay, B.; Haskó, G.; Gao, B.; Mackie, K.; Pacher, P. CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. Br. J. Pharmacol., 2010, 160(3), 657-668.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00769.x] [PMID: 20590569]
[27]
Lipina, C.; Hundal, H.S. Modulation of cellular redox homeostasis by the endocannabinoid system. Open Biol., 2016, 6(4)150276
[http://dx.doi.org/10.1098/rsob.150276] [PMID: 27248801]
[28]
Mukhopadhyay, P.; Rajesh, M.; Bátkai, S.; Patel, V.; Kashiwaya, Y.; Liaudet, L.; Evgenov, O.V.; Mackie, K.; Haskó, G.; Pacher, P. CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes. Cardiovasc. Res., 2010, 85(4), 773-784.
[http://dx.doi.org/10.1093/cvr/cvp369] [PMID: 19942623]
[29]
Vettor, R.; Pagano, C. The role of the endocannabinoid system in lipogenesis and fatty acid metabolism. Best Pract. Res. Clin. Endocrinol. Metab., 2009, 23(1), 51-63.
[http://dx.doi.org/10.1016/j.beem.2008.10.002] [PMID: 19285260]
[30]
Jorgačević, B.; Mladenović, D.; Ninković, M.; Prokić, V.; Stanković, M.N.; Aleksić, V.; Cerović, I.; Vukićević, R.J.; Vučević, D.; Stanković, M.; Radosavljević, T. Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease. Hum. Exp. Toxicol., 2014, 33(7), 701-709.
[http://dx.doi.org/10.1177/0960327113506723] [PMID: 24130212]
[31]
Bermudez-Silva, F.J.; Cardinal, P.; Cota, D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J. Psychopharmacol. (Oxford), 2012, 26(1), 114-124.
[http://dx.doi.org/10.1177/0269881111408458] [PMID: 21824982]
[32]
Bartelt, A.; Orlando, P.; Mele, C.; Ligresti, A.; Toedter, K.; Scheja, L.; Heeren, J.; Di Marzo, V. Altered endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance. Diabetologia, 2011, 54(11), 2900-2910.
[http://dx.doi.org/10.1007/s00125-011-2274-6] [PMID: 21847582]
[33]
De Laurentiis, A.; Fernández Solari, J.; Mohn, C.; Zorrilla Zubilete, M.; Rettori, V. Endocannabinoid system participates in neuroendocrine control of homeostasis. Neuroimmunomodulation, 2010, 17(3), 153-156.
[http://dx.doi.org/10.1159/000258711] [PMID: 20134190]
[34]
Jalan, R.; Olde Damink, S.W.; Ter Steege, J.C.; Redhead, D.N.; Lee, A.; Hayes, P.C.; Deutz, N.E. Acute endotoxemia following transjugular intrahepatic stent-shunt insertion is associated with systemic and cerebral vasodilatation with increased whole body nitric oxide production in critically ill cirrhotic patients. J. Hepatol., 2011, 54(2), 265-271.
[http://dx.doi.org/10.1016/j.jhep.2010.06.042] [PMID: 21067839]
[35]
Pacher, P.; Kunos, G. Modulating the endocannabinoid system in human health and disease--successes and failures. FEBS J., 2013, 280(9), 1918-1943.
[http://dx.doi.org/10.1111/febs.12260] [PMID: 23551849]
[36]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[37]
Yuzefovych, L.V.; Musiyenko, S.I.; Wilson, G.L.; Rachek, L.I. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One, 2013, 8(1)e54059
[http://dx.doi.org/10.1371/journal.pone.0054059] [PMID: 23342074]
[38]
Ha, S.K.; Chae, C. Inducible nitric oxide distribution in the fatty liver of a mouse with high fat diet-induced obesity. Exp. Anim., 2010, 59(5), 595-604.
[http://dx.doi.org/10.1538/expanim.59.595] [PMID: 21030787]
[39]
Wu, G.; Fang, Y.Z.; Yang, S.; Lupton, J.R.; Turner, N.D. Glutathione metabolism and its implications for health. J. Nutr., 2004, 134(3), 489-492.
[http://dx.doi.org/10.1093/jn/134.3.489] [PMID: 14988435]
[40]
Nam, D.H.; Lee, M.H.; Kim, J.E.; Song, H.K.; Kang, Y.S.; Lee, J.E.; Kim, H.W.; Cha, J.J.; Hyun, Y.Y.; Kim, S.H.; Han, S.Y.; Han, K.H.; Han, J.Y.; Cha, D.R. Blockade of cannabinoid receptor 1 improves insulin resistance, lipid metabolism, and diabetic nephropathy in db/db mice. Endocrinology, 2012, 153(3), 1387-1396.
[http://dx.doi.org/10.1210/en.2011-1423] [PMID: 22234468]
[41]
Kunos, G.; Tam, J. The case for peripheral CB1 receptor blockade in the treatment of visceral obesity and its cardiometabolic complications. Br. J. Pharmacol., 2011, 163(7), 1423-1431.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01352.x] [PMID: 21434882]
[42]
Jourdan, T.; Djaouti, L.; Demizieux, L.; Gresti, J.; Vergès, B.; Degrace, P. CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes, 2010, 59(4), 926-934.
[http://dx.doi.org/10.2337/db09-1482] [PMID: 20110567]
[43]
DeLeve, L.D.; Wang, X.; Kanel, G.C.; Atkinson, R.D.; McCuskey, R.S. Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am. J. Pathol., 2008, 173(4), 993-1001.
[http://dx.doi.org/10.2353/ajpath.2008.070720] [PMID: 18772330]
[44]
Handa, P.; Thomas, S.; Morgan-Stevenson, V.; Maliken, B.D.; Gochanour, E.; Boukhar, S.; Yeh, M.M.; Kowdley, K.V. Iron alters macrophage polarization status and leads to steatohepatitis and fibrogenesis. J. Leukoc. Biol., 2019, 105(5), 1015-1026.
[http://dx.doi.org/10.1002/JLB.3A0318-108R] [PMID: 30835899]
[45]
Ahmed, U.; Latham, P.S.; Oates, P.S. Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis. World J. Gastroenterol., 2012, 18(34), 4651-4658.
[http://dx.doi.org/10.3748/wjg.v18.i34.4651] [PMID: 23002334]
[46]
Otogawa, K.; Kinoshita, K.; Fujii, H.; Sakabe, M.; Shiga, R.; Nakatani, K.; Ikeda, K.; Nakajima, Y.; Ikura, Y.; Ueda, M.; Arakawa, T.; Hato, F.; Kawada, N. Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: implications for the pathogenesis of human nonalcoholic steatohepatitis. Am. J. Pathol., 2007, 170(3), 967-980.
[http://dx.doi.org/10.2353/ajpath.2007.060441] [PMID: 17322381]
[47]
Miranda, K.; Mehrpouya-Bahrami, P.; Nagarkatti, P.S.; Nagarkatti, M. Cannabinoid receptor 1 blockade attenuates obesity and adipose tissue type 1 inflammation through miR-30e-5p regulation of delta-like-4 in macrophages and consequently downregulation of Th1 cells. Front. Immunol., 2019, 10, 1049.
[http://dx.doi.org/10.3389/fimmu.2019.01049] [PMID: 31134094]
[48]
Amano, S.U.; Cohen, J.L.; Vangala, P.; Tencerova, M.; Nicoloro, S.M.; Yawe, J.C.; Shen, Y.; Czech, M.P.; Aouadi, M. Local proliferation of macrophages contributes to obesity-associated adipose tissue inflammation. Cell Metab., 2014, 19(1), 162-171.
[http://dx.doi.org/10.1016/j.cmet.2013.11.017] [PMID: 24374218]
[49]
Boutens, L.; Stienstra, R. Adipose tissue macrophages: going off track during obesity. Diabetologia, 2016, 59(5), 879-894.
[http://dx.doi.org/10.1007/s00125-016-3904-9] [PMID: 26940592]
[50]
Morris, D.L.; Cho, K.W.; Delproposto, J.L.; Oatmen, K.E.; Geletka, L.M.; Martinez-Santibanez, G.; Singer, K.; Lumeng, C.N. Adipose tissue macrophages function as antigen-presenting cells and regulate adipose tissue CD4+ T cells in mice. Diabetes, 2013, 62(8), 2762-2772.
[http://dx.doi.org/10.2337/db12-1404] [PMID: 23493569]
[51]
Mehrpouya-Bahrami, P.; Chitrala, K.N.; Ganewatta, M.S.; Tang, C.; Murphy, E.A.; Enos, R.T.; Velazquez, K.T.; McCellan, J.; Nagarkatti, M.; Nagarkatti, P. Blockade of CB1 cannabinoid receptor alters gut microbiota and attenuates inflammation and diet-induced obesity. Sci. Rep., 2017, 7(1), 15645.
[http://dx.doi.org/10.1038/s41598-017-15154-6] [PMID: 29142285]
[52]
Guruharsha, K.G.; Kankel, M.W.; Artavanis-Tsakonas, S. The Notch signalling system: recent insights into the complexity of a conserved pathway. Nat. Rev. Genet., 2012, 13(9), 654-666.
[http://dx.doi.org/10.1038/nrg3272] [PMID: 22868267]
[53]
Nakano, T.; Fukuda, D.; Koga, J.; Aikawa, M. Delta-like Ligand 4-notch signaling in macrophage activation. Arterioscler. Thromb. Vasc. Biol., 2016, 36(10), 2038-2047.
[http://dx.doi.org/10.1161/ATVBAHA.116.306926] [PMID: 27562914]
[54]
Xu, H.; Zhu, J.; Smith, S.; Foldi, J.; Zhao, B.; Chung, A.Y.; Outtz, H.; Kitajewski, J.; Shi, C.; Weber, S.; Saftig, P.; Li, Y.; Ozato, K.; Blobel, C.P.; Ivashkiv, L.B.; Hu, X. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat. Immunol., 2012, 13(7), 642-650.
[http://dx.doi.org/10.1038/ni.2304] [PMID: 22610140]
[55]
Bi, P.; Shan, T.; Liu, W.; Yue, F.; Yang, X.; Liang, X.R.; Wang, J.; Li, J.; Carlesso, N.; Liu, X.; Kuang, S. Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat. Med., 2014, 20(8), 911-918.
[http://dx.doi.org/10.1038/nm.3615] [PMID: 25038826]
[56]
Skokos, D.; Nussenzweig, M.C. CD8- DCs induce IL-12-independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS. J. Exp. Med., 2007, 204(7), 1525-1531.
[http://dx.doi.org/10.1084/jem.20062305] [PMID: 17576775]
[57]
Amsen, D.; Blander, J.M.; Lee, G.R.; Tanigaki, K.; Honjo, T.; Flavell, R.A. Instruction of distinct CD4 T helper cell fates by different notch ligands on antigen-presenting cells. Cell, 2004, 117(4), 515-526.
[http://dx.doi.org/10.1016/S0092-8674(04)00451-9] [PMID: 15137944]
[58]
Pagotto, U.; Pasquali, R. Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors. Lancet, 2005, 365(9468), 1363-1364.
[http://dx.doi.org/10.1016/S0140-6736(05)66348-9] [PMID: 15836868]
[59]
Di Marzo, V.; Matias, I. Endocannabinoid control of food intake and energy balance. Nat. Neurosci., 2005, 8(5), 585-589.
[http://dx.doi.org/10.1038/nn1457] [PMID: 15856067]
[60]
Van Gaal, L.F.; Rissanen, A.M.; Scheen, A.J.; Ziegler, O.; Rössner, S. RIO-Europe Study Group Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet, 2005, 365(9468), 1389-1397.
[http://dx.doi.org/10.1016/S0140-6736(05)66374-X] [PMID: 15836887]
[61]
Després, J.P.; Golay, A.; Sjöström, L. Rimonabant in obesity-lipids study group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med., 2005, 353(20), 2121-2134.
[http://dx.doi.org/10.1056/NEJMoa044537] [PMID: 16291982]
[62]
Pi-Sunyer, F.X.; Aronne, L.J.; Heshmati, H.M.; Devin, J.; Rosenstock, J. RIO-North America study group Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA, 2006, 295(7), 761-775.
[http://dx.doi.org/10.1001/jama.295.7.761] [PMID: 16478899]
[63]
Scheen, A.J.; Finer, N.; Hollander, P.; Jensen, M.D.; Van Gaal, L.F. RIO-Diabetes Study Group Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet, 2006, 368(9548), 1660-1672.
[http://dx.doi.org/10.1016/S0140-6736(06)69571-8] [PMID: 17098084]
[64]
Cheung, B.M.Y.; Cheung, T.T.; Samaranayake, N.R. Safety of antiobesity drugs. Ther. Adv. Drug Saf., 2013, 4(4), 171-181.
[http://dx.doi.org/10.1177/2042098613489721] [PMID: 25114779]
[65]
Kenakin, T.P. Biased signalling and allosteric machines: new vistas and challenges for drug discovery. Br. J. Pharmacol., 2012, 165(6), 1659-1669.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01749.x] [PMID: 22023017]
[66]
Conn, P.J.; Lindsley, C.W.; Meiler, J.; Niswender, C.M. Opportunities and challenges in the discovery of allosteric modulators of GPCRs for treating CNS disorders. Nat. Rev. Drug Discov., 2014, 13(9), 692-708.
[http://dx.doi.org/10.1038/nrd4308] [PMID: 25176435]
[67]
Conn, P.J.; Christopoulos, A.; Lindsley, C.W. Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat. Rev. Drug Discov., 2009, 8(1), 41-54.
[http://dx.doi.org/10.1038/nrd2760] [PMID: 19116626]
[68]
Burford, N.T.; Clark, M.J.; Wehrman, T.S.; Gerritz, S.W.; Banks, M.; O’Connell, J.; Traynor, J.R.; Alt, A. Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proc. Natl. Acad. Sci. USA, 2013, 110(26), 10830-10835.
[http://dx.doi.org/10.1073/pnas.1300393110] [PMID: 23754417]
[69]
Wild, C.; Cunningham, K.A.; Zhou, J. Allosteric modulation of G proteincoupled receptors: an emerging approach of drug discovery. J. Pharmacol. Ther, 2013, 2, 1.
[PMID: 27148592]
[70]
Price, M.R.; Baillie, G.L.; Thomas, A.; Stevenson, L.A.; Easson, M.; Goodwin, R.; McLean, A.; McIntosh, L.; Goodwin, G.; Walker, G.; Westwood, P.; Marrs, J.; Thomson, F.; Cowley, P.; Christopoulos, A.; Pertwee, R.G.; Ross, R.A. Allosteric modulation of the cannabinoid CB1 receptor. Mol. Pharmacol., 2005, 68(5), 1484-1495.
[http://dx.doi.org/10.1124/mol.105.016162] [PMID: 16113085]
[71]
Ahn, K.H.; Mahmoud, M.M.; Kendall, D.A. Allosteric modulator ORG27569 induces CB1 cannabinoid receptor high affinity agonist binding state, receptor internalization, and Gi protein-independent ERK1/2 kinase activation. J. Biol. Chem., 2012, 287(15), 12070-12082.
[http://dx.doi.org/10.1074/jbc.M111.316463] [PMID: 22343625]
[72]
Turu, G.; Hunyady, L. Signal transduction of the CB1 cannabinoid receptor. J. Mol. Endocrinol., 2010, 44(2), 75-85.
[http://dx.doi.org/10.1677/JME-08-0190] [PMID: 19620237]
[73]
Wieckowska, A.; Papouchado, B.G.; Li, Z.; Lopez, R.; Zein, N.N.; Feldstein, A.E. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am. J. Gastroenterol., 2008, 103(6), 1372-1379.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01774.x] [PMID: 18510618]

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