The role of endocannabinoids system in fatty liver disease and therapeutic potentials

Saudi Journal of Gastroenterology

Volumn 19, Issue 4, 2013, Pages 144-151

  Alswat, Khalid A ^a  

^a KING SAUD UNIVERSITY   (Saudi Arabia)

Author keywords

Cannabinoid receptors type 1; cannabinoid receptors type 2; endocannabinoids; endocannabinoids system; fatty liver disease

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR;

ALCOHOLIC FATTY LIVER; BODY WEIGHT; DEGRADATION; FIBROGENESIS; HOMEOSTASIS; HUMAN; INSULIN RESISTANCE; LIPID DIET; LIPOGENESIS; METABOLIC SYNDROME X; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; REVIEW;

ANIMALS; ENDOCANNABINOIDS; FATTY LIVER; HUMANS; LIVER; RECEPTORS, CANNABINOID;

EID: 84880971915     PISSN: 13193767     EISSN: 19984049     Source Type: Journal    
DOI: 10.4103/1319-3767.114505     Document Type: Review

References (84)

1. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity. Gastroenterology 1999;116:1413-9
2. Vernon G, Baranova A, Younossi ZM. Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011;34:274-85
3. Lee JY, Kim KM, Lee SG, Yu E, Lim YS, Lee HC, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: A review of 589 consecutive liver biopsies in a single center. J Hepatol 2007;47:239-44
4. Marcos A, Fisher RA, Ham JM, Olzinski AT, Shiffman ML, Sanyal AJ, et al. Selection and outcome of living donors for adult to adult right lobe transplantation. Transplantation 2000;69:2410-5
5. Al-hamoudi W, El-Sabbah M, Ali S, Altuwaijri M, Bedewi M, Adam M, et al. Epidemiological, clinical, and biochemical characteristics of Saudi patients with nonalcoholic fatty liver disease: A hospital-based study. Ann Saudi Med 2012;32:288-92
6. Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007;11:1-16, vii
7. Ratziu V, Poynard T. Assessing the outcome of nonalcoholic steatohepatitis? It's time to get serious. Hepatology 2006;44:802-5
8. Purohit V, Rapaka R, Shurtleff D. Role of cannabinoids in the development of fatty liver (steatosis). AAPS J 2010;12:233-7
9. Mallat A, Lotersztajn S. Endocannabinoids and their role in fatty liver disease. Dig Dis 2010;28:261-6
10. Pertwee RG. Cannabinoid receptors and pain. Prog Neurobiol 2001;63:569-611
11. Costa B, Colleoni M, Conti S, Parolaro D, Franke C, Trovato AE, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol 2004;369:294-9
12. Mechoulam R, Parker LA, Gallily R. Cannabidiol: An overview of some pharmacological aspects. J Clin Pharmacol 2002;42(11 Suppl 1):11S-9
13. Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, et al. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology 2004;29:417-26
14. Leweke FM, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkotter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Pshychiatry 2012;2:e94
15. Guzmán M. Cannabinoids: Potential anticancer agents. Nat Rev Cancer 2003;3:74555
16. Mallat A, Lotersztajn S. Endocannabinoids and liver disease. I Endocannabinoids and their receptors in the liver. Am J Physiol Gastrointest Liver Physiol 2008;294:G9-12
17. Mallat A, Teixeira-Clerc F, Deveaux V, Lotersztajn S. Cannabinoid receptors as new targets of antifibrosing strategies during chronic liver diseases. Expert Opin Ther Targets 2007;11:403-9
18. Pacher P, Bátkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006;58:389-462
19. Pertwee RG. Cannabinoid pharmacology: The first 66 years. Br J Pharmacol 2006;147 Suppl 1:S163-71
20. Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964;86:1646
21. Mechoulam R, Peters M, Murillo-Rodriguez E, Hanus LO. Cannabidiol: Recent advances. Chem Biodivers 2007;4:1678-92
22. Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA, et al. International union of pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002;54:161-202
23. Devane WA, Dysarz FA 3rd, Johnson MR, Melvin LS, Howlett AC. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988;34:605-13
24. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990;346:5614
25. Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 2005;310:329-32
26. Mackie K. Cannabinoid receptors: Where they are and what they do. J Neuroendocrinol 2008;20 Suppl 1:10-4
27. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997;74:129-80
28. Shoemaker JL, Seely KA, Reed RL, Crow JP, Prather PL. The CB2 cannabinoid agonist AM-1241 prolongs survival in a transgenic mouse model of amyotrophic lateral sclerosis when initiated at symptom onset. J Neurochem 2007;101:87-98
29. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992;258:1946-9
30. Gabbay E, Avraham Y, Ilan Y, Israeli E, Berry EM. Endocannabinoids and liver disease: Review. Liver Int 2005;25:921-6
31. McKinney MK, Cravatt BF. Structure and function of fatty acid amide hydrolase. Annu Rev Biochem 2005;74:411-32
32. Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, et al. Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci U S A 2002;99:10819-24
33. Galiègue S, Mary S, Marchand J, Dussossoy D, Carrière D, Carayon P, et al. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 1995;232:54-61
34. Jeong WI, Osei-Hyiaman D, Park O, Liu J, Bátkai S, Mukhopadhyay P, et al. Paracrine activation of hepatic CB1 receptors by stellate cell-derived endocannabinoids mediates alcoholic fatty liver. Cell Metab 2008;7:227-35
35. Moezi L, Gaskari SA, Liu H, Baik SK, Dehpour AR, Lee SS. Anandamide mediates hyperdynamic circulation in cirrhotic rats via CB (1) and VR (1) receptors. Br J Pharmacol 2006;149:898-908
36. Bátkai S, Járai Z, Wagner JA, Goparaju SK, Varga K, Liu J, et al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med 2001;7:827-32
37. Ros J, Clària J, To-Figueras J, Planagumà A, Cejudo-Martin P, Fernandez-Varo G, et al. Endogenous cannabinoids: A new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 2002;122:85-93
38. Cota D. CB1 receptors: Emerging evidence for central and peripheral mechanisms that regulate energy balance, metabolism, and cardiovascular health. Diabetes Metab Res Rev 2007;23:507-17
39. Marco EM, Romero-Zerbo SY, Viveros MP, Bermudez-Silva FJ. The role of the endocannabinoid system in eating disorders: Pharmacological implications. Behav Pharmacol 2012;23:526-36
40. Bermudez-Silva FJ, Cardinal P, Cota D. The role of the endocannabinoid system in the neuroendocrine regulation of energy balance. J Psychopharmacol 2012;26:114-24
41. Kirkham TC, Williams CM, Fezza F, Di Marzo V. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol 2002;136:550-7
42. Ravinet Trillou C, Delgorge C, Menet C, Arnone M, Soubrié P. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. Int J Obes Relat Metab Disord 2004;28:640-8
43. Ravinet Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP, et al. Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003;284:R345-53
44. Cota D, Marsicano G, Tschöp M, Grübler Y, Flachskamm C, Schubert M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest 2003;112:423-31
45. Brown MS, Goldstein JL. Sterol regulatory element binding proteins (SREBPs): Controllers of lipid synthesis and cellular uptake. Nutr Rev 1998;56:S1-3
46. Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000;288:2379-81
47. Kim EK, Miller I, Landree LE, Borisy-Rudin FF, Brown P, Tihan T, et al. Expression of FAS within hypothalamic neurons: A model for decreased food intake after C75 treatment. Am J Physiol Endocrinol Metab 2002;283:E867-79
48. Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005;115:1298-305
49. 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;59:926-34
50. Osei-Hyiaman D, Liu J, Zhou L, Godlewski G, Harvey-White J, Jeong WI, et al. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 2008;118:3160-9
51. Gary-Bobo M, Elachouri G, Gallas JF, Janiak P, Marini P, Ravinet-Trillou C, et al. Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology 2007;46:122-9
52. You M, Fischer M, Deeg MA, Crabb DW. Ethanol induces fatty acid synthesis pathways by activation of sterol regulatory element-binding protein (SREBP). J Biol Chem 2002;277:29342-7
53. Blüher M, Engeli S, Klöting N, Berndt J, Fasshauer M, Bátkai S, et al. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006;55:3053-60
54. Côté M, Matias I, Lemieux I, Petrosino S, Alméras N, Després JP, et al. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 2007;31:692-9
55. Di Marzo V, Côté M, Matias I, Lemieux I, Arsenault BJ, Cartier A, et al. Changes in plasma endocannabinoid levels in viscerally obese men following a 1 year lifestyle modification programme and waist circumference reduction: Associations with changes in metabolic risk factors. Diabetologia 2009;52:213-7
56. Matias I, Gonthier MP, Orlando P, Martiadis V, De Petrocellis L, Cervino C, et al. Regulation, function, and dysregulation of endocannabinoids in models of adipose and beta-pancreatic cells and in obesity and hyperglycemia. J Clin Endocrinol Metab 2006;91:3171-80
57. Westerbacka J, Kotronen A, Fielding BA, Wahren J, Hodson L, Perttilä J, et al. Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease. Gastroenterology 2010;139:1961-1971.e1
58. Hézode C, Zafrani ES, Roudot-Thoraval F, Costentin C, Hessami A, Bouvier-Alias M, et al. Daily cannabis use: A novel risk factor of steatosis severity in patients with chronic hepatitis C. Gastroenterology 2008;134:432-9
59. van der Poorten D, Shahidi M, Tay E, Sesha J, Tran K, McLeod D, et al. Hepatitis C virus induces the cannabinoid receptor 1. PLoS One 2010;5:e12841
60. Pi-Sunyer FX, Aronne LJ, Heshmati HM, 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;295:761-75
61. Van Gaal LF, Rissanen AM, Scheen AJ, 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;365:1389-97
62. Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal LF, RIO-Diabetes Study Group. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: A randomised controlled study. Lancet 2006;368:1660-72
63. Després JP, 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;353:2121-34
64. Rosenstock J, Iranmanesh A, Hollander PA. Improved glycemic control with weight loss plus beneficial effects on atherogenic dyslipidemia with rimonabant in drug-naive type 2 diabetes: The Serenade trial. Diabetes 2007;56:A49-50
65. Nissen SE, Nicholls SJ, Wolski K, Rodes-Cabau J, Cannon CP, Deanfield JE, et al. Effect of rimonabant on progression of atherosclerosis in patients with abdominal obesity and coronary artery disease: The STRADIVARIUS randomized controlled trial. JAMA 2008;299:1547-60
66. Hollander PA, Amod A, Litwak LE, Chaudhari U. ARPEGGIO Study Group. Effect of rimonabant on glycemic control in insulin-treated type 2 diabetes: The ARPEGGIO trial. Diabetes Care 2010;33:605-7
67. Després JP, Ross R, Boka G, Alméras N, Lemieux I, ADAGIO-Lipids Investigators. Effect of rimonabant on the high-triglyceride/ low-HDL-cholesterol dyslipidemia, intraabdominal adiposity, and liver fat: The ADAGIO-Lipids trial. Arterioscler Thromb Vasc Biol 2009;29:416-23
68. Christopoulou FD, Kiortsis DN. An overview of the metabolic effects of rimonabant in randomized controlled trials: Potential for other cannabinoid 1 receptor blockers in obesity. J Clin Pharm Ther 2011;36:10-8
69. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: A meta-analysis of randomised trials. Lancet 2007;370:1706-13
70. Sam AH, Salem V, Ghatei MA. Rimonabant: From RIO to Ban. J Obes 2011;2011:432607
71. Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005;128:742-55
72. Bátkai S, Osei-Hyiaman D, Pan H, El-Assal O, Rajesh M, Mukhopadhyay P, et al. Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J 2007;21:1788-800
73. Lotersztajn S, Teixeira-Clerc F, Julien B, Deveaux V, Ichigotani Y, Manin S, et al. CB2 receptors as new therapeutic targets for liver diseases. Br J Pharmacol 2008;153:286-9
74. Deveaux V, Cadoudal T, Ichigotani Y, Teixeira-Clerc F, Louvet A, Manin S, et al. Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS One 2009;4:e5844
75. Agudo J, Martin M, Roca C, Molas M, Bura AS, Zimmer A, et al. Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia 2010;53:2629-40
76. Mendez-Sanchez N, Zamora-Valdes D, Pichardo-Bahena R, Barredo-Prieto B, Ponciano-Rodriguez G, Bermejo-Martinez L, et al. Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease. Liver Int 2007;27:215-9
77. Teixeira-Clerc F, Julien B, Grenard P, Tran Van Nhieu J, Deveaux V, Li L, et al. CB1 cannabinoid receptor antagonism: A new strategy for the treatment of liver fibrosis. Nat Med 2006;12:671-6
78. Munoz-Luque J, Ros J, Fernandez-Varo G, Tugues S, Morales-Ruiz M, Alvarez CE, et al. Regression of fibrosis after chronic stimulation of cannabinoid CB2 receptor in cirrhotic rats. J Pharmacol Exp Ther 2008;324:475-83
79. Teixeira-Clerc F, Belot MP, Manin S, Deveaux V, Cadoudal T, Chobert MN, et al. Beneficial paracrine effects of cannabinoid receptor 2 on liver injury and regeneration. Hepatology 2010;52:1046-59
80. No author listed. Phase 1 pharmacokinetic study of CP-945598. Clincial trials. Gov identifier: NCT00706537. Available from: Http://clinicaltrials. gov/ct2/show/NCT00706537?term=Cannabinoid and rank=73. [Last accessed on 2013 Apr 10].
81. No author listed. Study to assess the effect of cannabidiol on liver fat levels in subjects with fatty liver disease. Clinical trials gov. Identifier: NCT01284634. Available from: Http://clinicaltrials.gov/ct2/show/ NCT01284634?term=cannabidiol and rank=5. [Last accessed on 2013 Apr 10].
82. No author listed. GWMD1092-GW42003: GW42004 Together plus alone in type II diabetes. Clinical Trial gov. Identifier: NCT01217112. Available from: Http://clinicaltrials.gov/ct2/show/NCT01217112. [Last accessed on 2013 Apr 10].
83. Selvarajah D, Gandhi R, Emery CJ, Tesfaye S. Randomized placebo-controlled double-blind clinical trial of cannabis-based medicinal product (Sativex) in painful diabetic neuropathy: Depression is a major confounding factor. Diabetes Care 2010;33:128-30
84. Collin C, Ehler E, Waberzinek G, Alsindi Z, Davies P, Powell K, et al. A double-blind, randomized, placebo-controlled, parallel-group study of Sativex, in subjects with symptoms of spasticity due to multiple sclerosis. Neurol Res 2010;32:451-9