The role of the endocannabinoid system in skeletal muscle and metabolic adaptations to exercise: Potential implications for the treatment of obesity

Obesity Reviews

Volumn 13, Issue 12, 2012, Pages 1110-1124

  Heyman, E ^a   Gamelin, F X ^a   Aucouturier, J ^a   Di Marzo, V ^b  

^a UNIV LILLE   (France)

^b CNR   (Italy)

Author keywords

Endocannabinoid system; Exercise; Obesity; Skeletal muscle

Indexed keywords

CANNABINOID 1 RECEPTOR; ENDOCANNABINOID; FATTY ACID; GLUCOSE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RIMONABANT; VANILLOID RECEPTOR 1;

EXERCISE; HUMAN; METABOLISM; OBESITY; PROTEIN EXPRESSION; REVIEW; SKELETAL MUSCLE;

ADAPTATION, PHYSIOLOGICAL; CANNABINOID RECEPTOR ANTAGONISTS; CANNABINOID RECEPTOR MODULATORS; ENDOCANNABINOIDS; ENERGY METABOLISM; EXERCISE; HOMEOSTASIS; HUMANS; MUSCLE, SKELETAL; OBESITY; RECEPTOR, CANNABINOID, CB1; RECEPTORS, CANNABINOID;

EID: 84868514599     PISSN: 14677881     EISSN: 1467789X     Source Type: Journal    
DOI: 10.1111/j.1467-789X.2012.01026.x     Document Type: Review

References (119)

1. Newman Z, Malik P, Wu TY, Ochoa C, Watsa N, Lindgren C. Endocannabinoids mediate muscarine-induced synaptic depression at the vertebrate neuromuscular junction. Eur J Neurosci 2007; 25: 1619-1630.
2. Cadas H, Gaillet S, Beltramo M, Venance L, Piomelli D. Biosynthesis of an endogenous cannabinoid precursor in neurons and its control by calcium and cAMP. J Neurosci 1996; 16: 3934-3942.
3. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev 2006; 27: 73-100.
4. Dainese E, Oddi S, Maccarrone M. Interaction of endocannabinoid receptors with biological membranes. Curr Med Chem 2010; 17: 1487-1499.
5. Petrosino S, Ligresti A, Di Marzo V. Endocannabinoid chemical biology: a tool for the development of novel therapies. Curr Opin Chem Biol 2009; 13: 309-320.
6. Placzek EA, Okamoto Y, Ueda N, Barker EL. Membrane microdomains and metabolic pathways that define anandamide and 2-arachidonyl glycerol biosynthesis and breakdown. Neuropharmacology 2008; 55: 1095-1104.
7. McFarland MJ, Barker EL. Lipid rafts: a nexus for endocannabinoid signaling? Life Sci 2005; 77: 1640-1650.
8. Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci 2003; 4: 873-884.
9. Howlett AC, Barth F, Bonner TI etal. International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 2002; 54: 161-202.
10. Silvestri C, Ligresti A, Di Marzo V. Peripheral effects of endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle. Rev Endocr Metab Disord 2011; 12: 153-162.
11. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov 2004; 3: 771-784.
12. Bellocchio L, Lafenêtre P, Cannich A etal. Bimodal control of stimulated food intake by the endocannabinoid system. Nat Neurosci 2010; 13: 281-283.
13. Cavuoto P, Wittert GA. The role of the endocannabinoid system in the regulation of energy expenditure. Best Pract Res Clin Endocrinol Metab 2009; 23: 79-86.
14. Di Marzo V, Matias I. Endocannabinoid control of food intake and energy balance. Nat Neurosci 2005; 8: 585-589.
15. Maccarrone M, Gasperi V, Catani MV etal. The endocannabinoid system and its relevance for nutrition. Annu Rev Nutr 2010; 30: 423-440.
16. Poirier B, Bidouard JP, Cadrouvele C etal. The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes Metab 2005; 7: 65-72.
17. Jbilo O, Ravinet-Trillou C, Arnone M etal. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J 2005; 19: 1567-1569.
18. Nogueiras R, Diaz-Arteaga A, Lockie SH etal. The endocannabinoid system: role in glucose and energy metabolism. Pharmacol Res 2009; 60: 93-98.
19. Matias I, Petrosino S, Racioppi A, Capasso R, Izzo AA, Di Marzo V. Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity: effect of high fat diets. Mol Cell Endocrinol 2008; 286: S66-S78.
20. Blüher M, Engeli S, Klöting N etal. Dysregulation of the peripheral and adipose tissue endocannabinoid system in human abdominal obesity. Diabetes 2006; 55: 3053-3060.
21. Di Marzo V. The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008; 51: 1356-1367.
22. Matias I, Gonthier MP, Orlando P etal. 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: 3171-3180.
23. Zurlo F, Larson K, Bogardus C, Ravussin E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J Clin Invest 1990; 86: 1423-1427.
24. Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010; 2010: 476279.
25. Fujii N, Aschenbach WG, Musi N, Hirshman MF, Goodyear LJ. Regulation of glucose transport by the AMP-activated protein kinase. Proc Nutr Soc 2004; 63: 205-210.
26. Lesniak KT, Dubbert PM. Exercise and hypertension. Curr Opin Cardiol 2001; 16: 356-359.
27. Wood PD, Stefanick ML, Dreon DM etal. Changes in plasma lipids and lipoproteins in overweight men during weight loss through dieting as compared with exercise. N Engl J Med 1988; 319: 1173-1179.
28. Sparling PB, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A. Exercise activates the endocannabinoid system. Neuroreport 2003; 14: 2209-2211.
29. Heyman E, Gamelin FX, Goekint M etal. Intense exercise increases circulating endocannabinoid and BDNF levels in humans - possible implications for reward and depression. Psychoneuroendocrinology 2012; 37: 844-851.
30. Yan ZC, Liu DY, Zhang LL etal. Exercise reduces adipose tissue via cannabinoid receptor type 1 which is regulated by peroxisome proliferator-activated receptor-delta. Biochem Biophys Res Commun 2007; 354: 427-433.
31. Cavuoto P, McAinch AJ, Hatzinikolas G, Janovská A, Game P, Wittert GA. The expression of receptors for endocannabinoids in human and rodent skeletal muscle. Biochem Biophys Res Commun 2007; 364: 105-110.
32. Esposito I, Proto MC, Gazzerro P etal. The cannabinoid CB1 receptor antagonist rimonabant stimulates 2-deoxyglucose uptake in skeletal muscle cells by regulating the expression of phosphatidylinositol-3-kinase. Mol Pharmacol 2008; 74: 1678-1686.
33. Eckardt K, Sell H, Taube A etal. Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle. Diabetologia 2009; 52: 664-674.
34. Lipina C, Stretton C, Hastings S etal. Regulation of MAP kinase-directed mitogenic and protein kinase B-mediated signaling by cannabinoid receptor type 1 in skeletal muscle cells. Diabetes 2010; 59: 375-385.
35. Crespillo A, Suárez J, Bermúdez-Silva FJ etal. Expression of the cannabinoid system in muscle: effects of a high-fat diet and CB1 receptor blockade. Biochem J 2010; 433: 175-185.
36. Watkins BA, Hutchins H, Li Y, Seifert MF. The endocannabinoid signaling system: a marriage of PUFA and musculoskeletal health. J Nutr Biochem 2010; 21: 1141-1152.
37. Krylatov AV, Maslov LN, Lasukova OV, Pertwee RG. Cannabinoid receptor antagonists SR141716 and SR144528 exhibit properties of partial agonists in experiments on isolated perfused rat heart. Bull Exp Biol Med 2005; 139: 558-561.
38. Lindborg KA, Jacob S, Henriksen EJ. Effects of chronic antagonism of endocannabinoid-1 receptors on glucose tolerance and insulin action in skeletal muscles of lean and obese Zucker rats. Cardiorenal Med 2011; 1: 31-44.
39. Liu YL, Connoley IP, Wilson CA, Stock MJ. Effects of the cannabinoid CB1 receptor antagonist SR141716 on oxygen consumption and soleus muscle glucose uptake in Lep(ob)/Lep(ob) mice. Int J Obes (Lond) 2005; 29: 183-187.
40. Agudo J, Martin M, Roca C etal. Deficiency of CB2 cannabinoid receptor in mice improves insulin sensitivity but increases food intake and obesity with age. Diabetologia 2010; 53: 2629-2640.
41. Cavuoto P, McAinch AJ, Hatzinikolas G, Cameron-Smith D, Wittert GA. Effects of cannabinoid receptors on skeletal muscle oxidative pathways. Mol Cell Endocrinol 2007; 267: 63-69.
42. Hardie DG. Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 2011; 93: 891S-8916.
43. Rowles J, Scherer SW, Xi T etal. Cloning and characterization of PDK4 on 7q21.3 encoding a fourth pyruvate dehydrogenase kinase isoenzyme in human. J Biol Chem 1996; 271: 22376-22382.
44. Addy C, Wright H, Van Laere K etal. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metab 2008; 7: 68-78.
45. Kunz I, Meier MK, Bourson A, Fisseha M, Schilling W. Effects of rimonabant, a cannabinoid CB1 receptor ligand, on energy expenditure in lean rats. Int J Obes (Lond) 2008; 32: 863-870.
46. Herling AW, Kilp S, Elvert R, Haschke G, Kramer W. Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed Wistar rats. Endocrinology 2008; 149: 2557-2566.
47. Phielix E, Mensink M. Type 2 diabetes mellitus and skeletal muscle metabolic function. Physiol Behav 2008; 94: 252-258.
48. Osei-Hyiaman D, DePetrillo M, Pacher P etal. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005; 115: 1298-1305.
49. Lindborg KA, Teachey MK, Jacob S, Henriksen EJ. Effects of in vitro antagonism of endocannabinoid-1 receptors on the glucose transport system in normal and insulin-resistant rat skeletal muscle. Diabetes Obes Metab 2010; 12: 722-730.
50. Cote M, Matias I, Lemieux I etal. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int J Obes (Lond) 2007; 31: 692-699.
51. Phinney SD. Arachidonic acid maldistribution in obesity. Lipids 1996; 31(Suppl.): S271-S274.
52. Zygmunt PM, Petersson J, Andersson DA etal. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 1999; 400: 452-457.
53. Ross RA. Anandamide and vanilloid TRPV1 receptors. Br J Pharmacol 2003; 140: 790-801.
54. Bouaboula M, Hilairet S, Marchand J, Fajas L, Le Fur G, Casellas P. Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation. Eur J Pharmacol 2005; 517: 174-181.
55. Sun Y, Alexander SP, Garle MJ etal. Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism. Br J Pharmacol 2007; 152: 734-743.
56. O'Sullivan SE. Cannabinoids go nuclear: evidence for activation of peroxisome proliferator-activated receptors. Br J Pharmacol 2007; 152: 576-582.
57. Mackie K. Mechanisms of CB1 receptor signaling: endocannabinoid modulation of synaptic strength. Int J Obes (Lond) 2006; 30(Suppl. 1): S19-S23.
58. Sugiura T, Kishimoto S, Oka S, Gokoh M. Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog Lipid Res 2006; 45: 405-446.
59. Chabowski A, Zendzian-Piotrowska M, Nawrocki A, Gorski J. Not only accumulation, but also saturation status of intramuscular lipids is significantly affected by PPARγ activation. Acta Physiol (Oxf) 2012; 205: 145-158.
60. Grimaldi PA. Peroxisome proliferator-activated receptors as sensors of fatty acids and derivatives. Cell Mol Life Sci 2007; 64: 2459-2464.
61. Ehrenborg E, Krook A. Regulation of skeletal muscle physiology and metabolism by peroxisome proliferator-activated receptor delta. Pharmacol Rev 2009; 61: 373-393.
62. Lendoye E, Sibille B, Rousseau AS, Murdaca J, Grimaldi PA, Lopez P. PPARbeta activation induces rapid changes of both AMPK subunit expression and AMPK activation in mouse skeletal muscle. Mol Endocrinol 2011; 25: 1487-1498.
63. Di Marzo V, Cote M, Matias I etal. 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: 213-217.
64. Di Marzo V, Verrijken A, Hakkarainen A etal. Role of insulin as a negative regulator of plasma endocannabinoid levels in obese and nonobese subjects. Eur J Endocrinol 2009; 161: 715-722.
65. Tedesco L, Valerio A, Dossena M etal. Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways. Diabetes 2010; 59: 2826-2836.
66. Luo Z, Ma L, Zhao Z etal. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1alpha upregulation in mice. Cell Res 2012; 22: 551-564.
67. Feuerecker M, Hauer D, Toth R etal. Effects of exercise stress on the endocannabinoid system in humans under field conditions. Eur J Appl Physiol 2012; 112: 2777-2781.
68. Raichlen DA, Foster AD, Gerdeman GL, Seillier A, Giuffrida A. Wired to run: exercise-induced endocannabinoid signaling in humans and cursorial mammals with implications for the 'runner's high'. J Exp Biol 2012; 215: 1331-1336.
69. Dietrich A, McDaniel WF. Endocannabinoids and exercise. Br J Sports Med 2004; 38: 536-541.
70. Hill MN, Titterness AK, Morrish AC etal. Endogenous cannabinoid signaling is required for voluntary exercise-induced enhancement of progenitor cell proliferation in the hippocampus. Hippocampus 2010; 20: 513-523.
71. Hill MN, McEwen BS. Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 791-797.
72. Hill MN, Karatsoreos IN, Hillard CJ, McEwen BS. Rapid elevations in limbic endocannabinoid content by glucocorticoid hormones in vivo. Psychoneuroendocrinology 2010; 35: 1333-1338.
73. Murdolo G, Kempf K, Hammarstedt A, Herder C, Smith U, Jansson PA. Insulin differentially modulates the peripheral endocannabinoid system in human subcutaneous abdominal adipose tissue from lean and obese individuals. J Endocrinol Invest 2007; 30: RC17-RC21.
74. Di Marzo V, Piscitelli F, Mechoulam R. Cannabinoids and endocannabinoids in metabolic disorders with focus on diabetes. Handb Exp Pharmacol 2011; 203: 75-104.
75. Robitaille M, Dubé MC, Weisnagel SJ etal. Substrate source utilization during moderate intensity exercise with glucose ingestion in type 1 diabetic patients. J Appl Physiol 2007; 103: 119-124.
76. Bonen A, Belcastro AN, MacIntyre K, Gardner J. Hormonal responses during intense exercise preceded by glucose ingestion. Can J Appl Sport Sci 1980; 5: 85-90.
77. Richter EA, Galbo H, Sonne B, Holst JJ, Christensen NJ. Adrenal medullary control of muscular and hepatic glycogenolysis and of pancreatic hormonal secretion in exercising rats. Acta Physiol Scand 1980; 108: 235-242.
78. Heyman E, Delamarche P, Berthon P etal. Alteration in sympathoadrenergic activity at rest and during intense exercise despite normal aerobic fitness in late pubertal adolescent girls with type 1 diabetes. Diabetes Metab 2007; 33: 422-429.
79. Jamurtas AZ, Tofas T, Fatouros I etal. The effects of low and high glycemic index foods on exercise performance and beta-endorphin responses. J Int Soc Sports Nutr 2011; 8: 15.
80. Riebe CJ, Wotjak CT. Endocannabinoids and stress. Stress 2011; 14: 384-397.
81. Jeukendrup AE. Modulation of carbohydrate and fat utilization by diet, exercise and environment. Biochem Soc Trans 2003; 31: 1270-1273.
82. Egan B, Carson BP, Garcia-Roves PM etal. Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor coactivator-1 mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle. J Physiol 2010; 588: 1779-1790.
83. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003; 24: 78-90.
84. Fu J, Gaetani S, Oveisi F etal. Oleylethanolamide regulates feeding and body weight through activation of the nuclear receptor PPAR-alpha. Nature 2003; 425: 90-93.
85. Hansen HS, Diep TA. N-acylethanolamines, anandamide and food intake. Biochem Pharmacol 2009; 78: 553-560.
86. Thabuis C, Tissot-Favre D, Bezelgues JB etal. Biological functions and metabolism of oleoylethanolamide. Lipids 2008; 43: 887-894.
87. Guzman M, Lo Verme J, Fu J, Oveisi F, Blázquez C, Piomelli D. Oleoylethanolamide stimulates lipolysis by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR-alpha). J Biol Chem 2004; 279: 27849-27854.
88. Bermúdez-Silva FJ, Suarez J, Baixeras E etal. Presence of functional cannabinoid receptors in human endocrine pancreas. Diabetologia 2008; 51: 476-487.
89. Li C, Bowe JE, Jones PM, Persaud SJ. Expression and function of cannabinoid receptors in mouse islets. Islets 2010; 2: 293-302.
90. Li C, Jones PM, Persaud SJ. Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. Pharmacol Ther 2011; 129: 307-320.
91. You T, Disanzo BL, Wang X, Yang R, Gong D. Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise. Lipids Health Dis 2011; 10: 194.
92. Kiens B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev 2006; 86: 205-243.
93. Houmard JA. Intramuscular lipid oxidation and obesity. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1111-R1116.
94. Hood DA, Irrcher I, Ljubicic V, Joseph AM. Coordination of metabolic plasticity in skeletal muscle. J Exp Biol 2006; 209: 2265-2275.
95. Lavoie JM, Gauthier MS. Regulation of fat metabolism in the liver: link to non-alcoholic hepatic steatosis and impact of physical exercise. Cell Mol Life Sci 2006; 63: 1393-1409.
96. Flowers MT, Ntambi JM. Stearoyl-CoA desaturase and its relation to high-carbohydrate diets and obesity. Biochim Biophys Acta 2009; 1791: 85-91.
97. Osei-Hyiaman D, Liu J, Zhou L etal. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest 2008; 118: 3160-3169.
98. Yasari S, Prud'homme D, Tesson F etal. Effects of exercise training on molecular markers of lipogenesis and lipid partitioning in fructose-induced liver fat accumulation. J Nutr Metab 2012; 2012: 181687.
99. Gomes da Silva S, Araujo BH, Cossa AC etal. Physical exercise in adolescence changes CB1 cannabinoid receptor expression in the rat brain. Neurochem Int 2010; 57: 492-496.
100. De Chiara V, Errico F, Musella A etal. Voluntary exercise and sucrose consumption enhance cannabinoid CB1 receptor sensitivity in the striatum. Neuropsychopharmacology 2010; 35: 374-387.
101. Wolf SA, Bick-Sander A, Fabel K etal. Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal 2010; 17: 8-12.
102. Dubreucq S, Koehl M, Abrous DN, Marsicano G, Chaouloff F. CB1 receptor deficiency decreases wheel-running activity: consequences on emotional behaviours and hippocampal neurogenesis. Exp Neurol 2010; 224: 106-113.
103. Fuss J, Gass P. Endocannabinoids and voluntary activity in mice: runner's high and long-term consequences in emotional behaviors. Exp Neurol 2010; 224: 103-105.
104. Huerta M, Ortiz-Mesina M, Trujillo X etal. Effects of cannabinoids on caffeine contractures in slow and fast skeletal muscle fibers of the frog. J Membr Biol 2009; 229: 91-99.
105. Alptekin A, Galadari S, Shuba Y, Petroianu G, Oz M. The effects of anandamide transport inhibitor AM404 on voltage-dependent calcium channels. Eur J Pharmacol 2010; 634: 10-15.
106. Mahmmoud Y, Gaster M. Uncoupling of sarcoplasmic reticulum Ca(2+) -ATPase by N-arachidonoyl dopamine. Members of the endocannabinoid family as thermogenic drugs. Br J Pharmacol 2012; 166: 2060-2069.
107. El Manira A, Kyriakatos A. The role of endocannabinoid signaling in motor control. Physiology (Bethesda) 2010; 25: 230-238.
108. Chaouloff F, Dubreucq S, Bellocchio L, Marsicano G. Endocannabinoids and motor behavior: CB1 receptors also control running activity. Physiology (Bethesda) 2011; 26: 76-77; author reply 78.
109. Garland T Jr, Schutz H, Chappell MA etal. The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives. J Exp Biol 2011; 214: 206-229.
110. Maldonado R, Valverde O, Berrendero F. Involvement of the endocannabinoid system in drug addiction. Trends Neurosci 2006; 29: 225-232.
111. Yu HL, Deng XQ, Li YJ, Li YC, Quan ZS, Sun XY. N-palmitoylethanolamide, an endocannabinoid, exhibits antidepressant effects in the forced swim test and the tail suspension test in mice. Pharmacol Rep 2011; 63: 834-839.
112. Hayase T. Differential effects of TRPV1 receptor ligands against nicotine-induced depression-like behaviors. BMC Pharmacol 2011; 18: 11-16.
113. Scheen AJ, Rorive M, Letiexhe M. Physical exercise for preventing obesity, promoting weight loss and maintaining weight management. Rev Med Liege 2001; 56: 244-247.
114. Akbas F, Gasteyger C, Sjodin A, Astrup A, Larsen TM. A critical review of the cannabinoid receptor as a drug target for obesity management. Obes Rev 2009; 10: 58-67.
115. Bermudez-Silva FJ, Viveros MP, McPartland JM, Rodriguez de Fonseca F. The endocannabinoid system, eating behavior and energy homeostasis: the end or a new beginning? Pharmacol Biochem Behav 2010; 95: 375-382.
116. Hills AP, Shultz SP, Soares MJ etal. Resistance training for obese, type 2 diabetic adults: a review of the evidence. Obes Rev 2010; 11: 740-749.
117. Chang C, Liu W, Zhao X, Li S, Yu C. Effect of supervised exercise intervention on metabolic risk factors and physical fitness in Chinese obese children in early puberty. Obes Rev 2008; 9(Suppl. 1): 135-141.
118. Brownell KD. Exercise and obesity treatment: psychological aspects. Int J Obes Relat Metab Disord 1995; 19(Suppl. 4): S122-S125.
119. Lavie CJ, Milani RV. Effects of cardiac rehabilitation, exercise training, and weight reduction on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in obese coronary patients. Am J Cardiol 1997; 79: 397-401.