The endocannabinoid system as a key mediator during liver diseases: New insights and therapeutic openings

British Journal of Pharmacology

Volumn 163, Issue 7, 2011, Pages 1432-1440

  Mallat, A ^a,b,c   Teixeira Clerc, F ^a,b   Deveaux, V ^a,b   Manin, S ^a,b   Lotersztajn, S ^a,b,c  

^a INSERM U955   (France)

^b FACULTÉ DE MÉDECINE   (France)

^c HENRI MONDOR HOSPITAL   (France)

Author keywords

alcoholic liver disease; cannabinoid receptor 1; cannabinoid receptor 2; hepatic inflammation; hepatic myofibroblasts; Kupffer cells; liver; liver fibrosis; non alcoholic fatty liver disease; steatosis

Indexed keywords

1 DEOXY 3 (1,1 DIMETHYLBUTYL) DELTA8 TETRAHYDROCANNABINOL; 2 ARACHIDONOYLGLYCEROL; AM 6545; ANANDAMIDE; ANGIOTENSIN 2 RECEPTOR; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR AGONIST; CANNABIS; CARBON TETRACHLORIDE; CONCANAVALIN A; DOPAMINE; ENDOCANNABINOID; FATTY ACID DERIVED ENDOCANNABINOID; OPIATE RECEPTOR; OREXIN; PHYTOCANNABINOID; PLACEBO; RIMONABANT; THIOACETAMIDE; UNCLASSIFIED DRUG; ADIPONECTIN; CANNABINOID RECEPTOR ANTAGONIST; DRONABINOL; TUMOR NECROSIS FACTOR ALPHA;

ALCOHOL LIVER DISEASE; ANTIINFLAMMATORY ACTIVITY; CHRONIC LIVER DISEASE; DISEASE ASSOCIATION; DISEASE COURSE; DRUG INHIBITION; FATTY LIVER; FIBROGENESIS; HEPATITIS; HUMAN; INSULIN RESISTANCE; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER INJURY; LIVER ISCHEMIA; LIVER PROTECTION; LIVER REGENERATION; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; ALCOHOL LIVER CIRRHOSIS; ALCOHOLIC FATTY LIVER; ASCITES; ATHEROSCLEROSIS; BINDING AFFINITY; CYTOKINE PRODUCTION; DISEASE SEVERITY; DRUG BIOAVAILABILITY; DRUG PENETRATION; DRUG RECEPTOR BINDING; DYSLIPIDEMIA; IMMUNOMODULATION; LIVER DISEASE; METABOLIC DISORDER; OSTEOPOROSIS; PORTAL HYPERTENSION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; STEATOSIS; UNSPECIFIED SIDE EFFECT;

ANIMALS; ENDOCANNABINOIDS; HUMANS; LIVER DISEASES; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2;

EID: 79960297797     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01397.x     Document Type: Review

References (69)

1. Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, et al,. (2010). Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia 53: 2629-2640.
2. Avraham Y, Israeli E, Gabbay E, Okun A, Zolotarev O, Silberman I, et al,. (2006). Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol Dis 21: 237-245. (Pubitemid 41817322)
3. Avraham Y, Zolotarev O, Grigoriadis NC, Poutahidis T, Magen I, Vorobiav L, et al,. (2008). Cannabinoids and capsaicin improve liver function following thioacetamide-induced acute injury in mice. Am J Gastroenterol 103: 3047-3056.
4. Batkai S, Jarai Z, Wagner JA, Goparaju SK, Varga K, Liu J, et al,. (2001). Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 7: 827-832. (Pubitemid 32691638)
5. Batkai S, Mukhopadhyay P, Harvey-White J, Kechrid R, Pacher P, Kunos G, (2007a). Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats. Am J Physiol Heart Circ Physiol 293: H2210-H2218.
6. Batkai S, Osei-Hyiaman D, Pan H, El-Assal O, Rajesh M, Mukhopadhyay P, et al,. (2007b). Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J 21: 1788-1800. (Pubitemid 46855625)
7. Bensaid M, Gary-Bobo M, Esclangon A, Maffrand JP, Le Fur G, Oury-Donat F, et al,. (2003). The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 63: 908-914. (Pubitemid 36368998)
8. Bluher M, Engeli S, Kloting N, Berndt J, Fasshauer M, Batkai S, et al,. (2006). Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 55: 3053-3060. (Pubitemid 44923642)
9. Cluny NL, Vemuri VK, Chambers AP, Limebeer CL, Bedard H, Wood JT, et al,. (2010). A novel peripherally restricted cannabinoid receptor antagonist, AM6545, reduces food intake and body weight, but does not cause malaise, in rodents. Br J Pharmacol 161: 629-642.
10. Cortez-Pinto H, de Moura MC, Day CP, (2006). Non-alcoholic steatohepatitis: from cell biology to clinical practice. J Hepatol 44: 197-208. (Pubitemid 41772535)
11. Cote M, Matias I, Lemieux I, Petrosino S, Almeras N, Despres JP, et al,. (2007). Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 31: 692-699. (Pubitemid 46482358)
12. Dagon Y, Avraham Y, Ilan Y, Mechoulam R, Berry EM, (2007). Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP-activated protein kinase. FASEB J 21: 2431-2441. (Pubitemid 47230673)
13. Defer N, Wan J, Souktani R, Escoubet B, Perier M, Caramelle P, et al,. (2009). The cannabinoid receptor type 2 promotes cardiac myocyte and fibroblast survival and protects against ischemia/reperfusion-induced cardiomyopathy. FASEB J 23: 2120-2130.
14. DeLeve LD, Wang X, Kanel GC, Atkinson RD, McCuskey RS, (2008). Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am J Pathol 173: 993-1001.
15. Despres JP, Golay A, Sjostrom L, (2005). Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353: 2121-2134. (Pubitemid 41653104)
16. Deveaux V, Cadoudal T, Ichigotani Y, Teixeira-Clerc F, Louvet A, Manin S, et al,. (2009). Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS ONE 4: e5844.
17. Di Marzo V, (2008). Targeting the endocannabinoid system: to enhance or reduce? Nat Rev Drug Discov 7: 438-455. (Pubitemid 351649182)
18. Di Marzo V, Bifulco M, De Petrocellis L, (2004). The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 3: 771-784. (Pubitemid 39242829)
19. Domenicali M, Caraceni P, Giannone F, Pertosa AM, Principe A, Zambruni A, et al,. (2009). Cannabinoid type 1 receptor antagonism delays ascites formation in rats with cirrhosis. Gastroenterology 137: 341-349.
20. Engeli S, Bohnke J, Feldpausch M, Gorzelniak K, Janke J, Batkai S, et al,. (2005). Activation of the peripheral endocannabinoid system in human obesity. Diabetes 54: 2838-2843. (Pubitemid 41401077)
21. Gary-Bobo M, Elachouri G, Gallas JF, Janiak P, Marini P, Ravinet-Trillou C, et al,. (2007). Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology 46: 122-129. (Pubitemid 47171928)
22. Gaskari SA, Liu H, Moezi L, Li Y, Baik SK, Lee SS, (2005). Role of endocannabinoids in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Br J Pharmacol 146: 315-323. (Pubitemid 41486673)
23. Hegde VL, Hegde S, Cravatt BF, Hofseth LJ, Nagarkatti M, Nagarkatti PS, (2008). Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells. Mol Pharmacol 74: 20-33. (Pubitemid 351872155)
24. Hezode C, Roudot-Thoraval F, Nguyen S, Grenard P, Julien B, Zafrani ES, et al,. (2005). Daily cannabis smoking as a risk factor for fibrosis progression in chronic hepatitis C. Hepatology 42: 63-71. (Pubitemid 40911312)
25. Hezode C, Zafrani ES, Roudot-Thoraval F, Costentin C, Hessami A, Bouvier-Alias M, et al,. (2008). Daily cannabis use, a novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology 134: 432-439. (Pubitemid 351173051)
26. Ishida JH, Peters MG, Jin C, Louie K, Tan V, Bacchetti P, et al,. (2008). Influence of cannabis use on severity of hepatitis C disease. Clin Gastroenterol Hepatol 6: 69-75. (Pubitemid 350309529)
27. Jeong WI, Osei-Hyiaman D, Park O, Liu J, Batkai S, Mukhopadhyay P, et al,. (2008). Paracrine activation of hepatic CB(1) receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab 7: 227-235. (Pubitemid 351285525)
28. Jourdan T, Djaouti L, Demizieux L, Gresti J, Verges B, Degrace P, (2010). CB1 antagonism exerts specific molecular effects on visceral and subcutaneous fat and reverses liver steatosis in diet-induced obese mice. Diabetes 59: 926-934.
29. Julien B, Grenard P, Teixeira-Clerc F, Tran-Van-Nhieu J, Li L, Karzak M, et al,. (2005). Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 128: 742-755. (Pubitemid 40585376)
30. Klein TW, (2005). Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 5: 400-411. (Pubitemid 40685989)
31. Kunos G, Osei-Hyiaman D, Batkai S, Sharkey KA, Makriyannis A, (2009). Should peripheral CB(1) cannabinoid receptors be selectively targeted for therapeutic gain? Trends Pharmacol Sci 30: 1-7.
32. Lotersztajn S, Julien B, Teixeira-Clerc F, Grenard P, Mallat A, (2005). Hepatic fibrosis: molecular mechanisms and drug targets. Ann Rev Pharmacol Toxicol 45: 605-628. (Pubitemid 40261819)
33. Lotersztajn S, Teixeira-Clerc F, Julien B, Deveaux V, Ichigotani Y, Manin S, et al,. (2008). CB2 receptors as new therapeutic targets during liver diseases. Br J Pharmacol 153: 286-289.
34. Louvet A, Teixeira-Clerc F, Deveaux V, Chobert MN, Pavoine C, Mallat A, et al,. (2010). Beneficial effects of cannabinoid receptor 2 on alcoholic liver disease. J Hepatology 52: S307-S308.
35. Lucey MR, Mathurin P, Morgan TR, (2009). Alcoholic hepatitis. N Engl J Med 360: 2758-2769.
36. Mallat A, Lotersztajn S, (2006). Endocannabinoids as novel mediators of liver diseases. J Endocrinol Invest 29: 58-65.
37. Mallat A, Lotersztajn S, (2008a). Cannabinoid receptors as therapeutic targets in the management of liver diseases. Drug News Perspect 21: 363-368.
38. Mallat A, Lotersztajn S, (2008b). Endocannabinoids and Their Receptors in the Liver. Am J Physiol Gastrointest Liver Physiol 294: G9-G12.
39. Mallat A, Lotersztajn S, (2010). Endocannabinoids and their role in fatty liver disease. Dig Dis 28: 261-266.
40. Mallat A, Teixeira-Clerc F, Deveaux V, Lotersztajn S, (2007). Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases. Expert Opin Ther Targets 11: 403-409. (Pubitemid 46290962)
41. Mandayam S, Jamal MM, Morgan TR, (2004). Epidemiology of alcoholic liver disease. Semin Liver Dis 24: 217-232. (Pubitemid 39167681)
42. Mandrekar P, Szabo G, (2009). Signalling pathways in alcohol-induced liver inflammation. J Hepatol 50: 1258-1266.
43. Moore SA, Nomikos GG, Dickason-Chesterfield AK, Schober DA, Schaus JM, Ying BP, et al,. (2005). From the cover: identification of a high-affinity binding site involved in the transport of endocannabinoids. Proc Natl Acad Sci USA 102: 17852-17857. (Pubitemid 41803586)
44. Mukhopadhyay B, Cinar R, Yin S, Liu J, Tam J, Godlewski G, et al,. (2011). Hyperactivation of anandamide synthesis and regulation of cell cycle progression via CB1 receptors in the regenerating liver. Proc Natl Acad Sci USA 108: 6323-6328.
45. Munoz-Luque J, Ros J, Fernandez-Varo G, Tugues S, Morales-Ruiz M, Alvarez CE, et al,. (2008). Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. J Pharmacol Exp Ther 324: 475-483. (Pubitemid 351185849)
46. Ofek O, Karsak M, Leclerc N, Fogel M, Frenkel B, Wright K, et al,. (2006). Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA 103: 696-701. (Pubitemid 43153088)
47. Ong JP, Younossi ZM, (2007). Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 11: 1-16. vii. (Pubitemid 46829973)
48. Osei-Hyiaman D, Depetrillo M, Pacher P, Liu J, Radaeva S, Batkai S, et al,. (2005). Endocannabinoid activation at hepatic CB(1) receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 115: 1298-1305. (Pubitemid 40629049)
49. Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J, Jeong WI, et al,. (2008). Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 118: 3160-3169.
50. Pacher P, Batkai S, Kunos G, (2006). The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 58: 389-462. (Pubitemid 44394908)
51. Parekh S, Anania FA, (2007). Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology 132: 2191-2207. (Pubitemid 46693752)
52. Patel KD, Davison JS, Pittman QJ, Sharkey KA, (2010). Cannabinoid CB(2) receptors in health and disease. Curr Med Chem 17: 1393-1410.
53. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, et al,. (2010). International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB and CB. Pharmacol Rev 62: 588-631.
54. Piomelli D, Giuffrida A, Calignano A, Rodriguez de Fonseca F, (2000). The endocannabinoid system as a target for therapeutic drugs. Trends Pharmacol Sci 21: 218-224. (Pubitemid 30331091)
55. van der Poorten D, Shahidi M, Tay E, Sesha J, Tran K, McLeod D, et al,. (2010). Hepatitis C virus induces the cannabinoid receptor 1. PLoS ONE 5: e12841.
56. Postic C, Girard J, (2008). Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 118: 829-838. (Pubitemid 351364588)
57. Ros J, Claria J, To-Figueras J, Planaguma A, Cejudo-Martin P, Fernandez-Varo G, et al,. (2002). Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 122: 85-93. (Pubitemid 34049198)
58. Servettaz A, Kavian N, Nicco C, Deveaux V, Chereau C, Wang A, et al,. (2010). Targeting the cannabinoid pathway limits the development of fibrosis and autoimmunity in a mouse model of systemic sclerosis. Am J Pathol 177: 187-196.
59. Siegmund SV, Uchinami H, Osawa Y, Brenner DA, Schwabe RF, (2005). Anandamide induces necrosis in primary hepatic stellate cells. Hepatology 41: 1085-1095. (Pubitemid 40593916)
60. Steffens S, Veillard NR, Arnaud C, Pelli G, Burger F, Staub C, et al,. (2005). Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434: 782-786. (Pubitemid 44739523)
61. Tam J, Vemuri VK, Liu J, Batkai S, Mukhopadhyay B, Godlewski G, et al,. (2010). Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest 120: 2953-2966.
62. Teixeira-Clerc F, Julien B, Grenard P, Tran-Van-Nhieu J, Deveaux V, Serriere-Lanneau V, et al,. (2006). CB1 cannabinoid receptor antagonism: a novel strategy for the treatment of liver fibrosis. Nat Med 12: 671-676. (Pubitemid 43865236)
63. Teixeira-Clerc F, Belot MP, Manin S, Deveaux V, Cadoudal T, Chobert MN, et al,. (2010). Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration. Hepatology 52: 1046-1059.
64. Tilg H, Moschen AR, (2010). Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52: 1836-1846.
65. Van Gaal LF, Scheen AJ, Rissanen AM, Rossner S, Hanotin C, Ziegler O, (2008). Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study. Eur Heart J 29: 1761-1771. (Pubitemid 352019811)
66. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, et al,. (2005). Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310: 329-332. (Pubitemid 41457202)
67. Westerbacka J, Kotronen A, Fielding BA, Wahren J, Hodson L, Perttila J, et al,. (2010). Splanchnic balance of free Fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic Fatty liver disease. Gastroenterology 139: 1961-1971. e1.
68. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ, (2003). The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 112: 91-100. (Pubitemid 38056380)
69. Yang YY, Lin HC, Huang YT, Lee TY, Hou MC, Wang YW, et al,. (2007). Effect of chronic CB1 cannabinoid receptor antagonism on livers of rats with biliary cirrhosis. Clin Sci (Lond) 112: 533-542.