Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 1 , Pages 17-32 , February 2009

The brain endocannabinoid system in the regulation of energy balance

  • Denis Richard (Professor, MF/CIHR Research Chair in Obesity)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 418 656 8711x3392.
  • ,
  • Benjamin Guesdon (Doctor, MF/CIHR Research Chair in Obesity)
  • ,
  • Elena Timofeeva (Doctor, MF/CIHR Research Chair in Obesity)

References 

  1. Pagotto U, Pasquali R. Endocannabinoids and energy metabolism. Journal of Endocrinological Investigation. 2006;29(3 Suppl):66–76
  2. Kunos G, Osei-Hyiaman D, Liu J et al. Endocannabinoids and the control of energy homeostasis. The Journal of Biological Chemistry, in press.
  3. Cota D. Role of the endocannabinoid system in energy balance regulation and obesity. Frontiers of Hormone Research. 2008;36:135–145
  4. Matias I, Cristino L, Di Marzo V. Endocannabinoids: some like it fat (and sweet too). Journal of Neuroendocrinology. 2008 May;20(Suppl. 1):100–109
  5. Woods SC. The endocannabinoid system: mechanisms behind metabolic homeostasis and imbalance. American Journal of Medicine. 2007 Feb;120(2 Suppl. 1):S9–17[Discussion S29–S32]
  6. Di Marzo V. Endocannabinoids: synthesis and degradation. Reviews of Physiology Biochemistry and Pharmacology. 2008;160:1–24
  7. Pagotto U, Vicennati V, Pasquali R. The endocannabinoid system and the treatment of obesity. Annals of Medicine. 2005;37(4):270–275
  8. Abizaid A, Horvath TL. Brain circuits regulating energy homeostasis. Regulatory Peptides. 2008 Aug 7;149(1–3):3–10
  9. Morton GJ, Cummings DE, Baskin DG, et al. Central nervous system control of food intake and body weight. Nature. 2006 Sep 21;443(7109):289–295
  10. Berthoud HR. Interactions between the ‘cognitive’ and ‘metabolic’ brain in the control of food intake. Physiology & Behavior. 2007 Aug 15;91(5):486–498
  11. Berthoud HR, Morrison C. The brain, appetite, and obesity. Annual Review of Psychology. 2008;59:55–92
  12. Blundell JE. Perspective on the central control of appetite. Obesity (Silver Spring). 2006 Jul;14(Suppl. 4):160S–163S
  13. Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating. Neuron. 2002 Oct 10;36(2):199–211
  14. Adan RA, Vanderschuren LJ, ElF S. Anti-obesity drugs and neural circuits of feeding. Trends in Pharmacological Sciences. 2008 Apr;29(4):208–217
  15. Kirkham TC, Williams CM, Fezza F, et al. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. British Journal of Pharmacology. 2002 Jun;136(4):550–557
  16. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001 Apr 12;410(6830):822–825
  17. Brown JE, Kassouny M, Cross JK. Kinetic studies of food intake and sucrose solution preference by rats treated with low doses of delta9-tetrahydrocannabinol. Behavioral Biology. 1977 May;20(1):104–110
  18. Williams CM, Rogers PJ, Kirkham TC. Hyperphagia in pre-fed rats following oral delta9-THC. Physiology & Behavior. 1998 Nov 15;65(2):343–346
  19. Cota D, Marsicano G, Tschop M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. The Journal of Clinical Investigation. 2003 Aug;112(3):423–431
  20. Ravinet Trillou C, Delgorge C, Menet C, et al. CB1 cannabinoid receptor knockout in mice leads to leanness, resistance to diet-induced obesity and enhanced leptin sensitivity. International Journal of Obesity and Related Metabolic Disorders. 2004 Apr;28(4):640–648
  21. Arnone M, Maruani J, Chaperon F, et al. Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology. 1997 Jul;132(1):104–106
  22. Jbilo O, Ravinet-Trillou C, Arnone M, et al. The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. The FASEB journal. 2005 Sep;19(11):1567–1569
  23. Wiley JL, Burston JJ, Leggett DC, et al. CB1 cannabinoid receptor-mediated modulation of food intake in mice. British Journal of Pharmacology. 2005 Jun;145(3):293–300
  24. Doyon C, Denis RG, Baraboi ED, et al. Effects of rimonabant (SR141716) on fasting-induced hypothalamic-pituitary-adrenal axis and neuronal activation in lean and obese Zucker rats. Diabetes. 2006 Dec;55(12):3403–3410
  25. Herling AW, Kilp S, Elvert R, et al. Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats. Endocrinology. 2008 May;149(5):2557–2566
  26. Kunz I, Meier MK, Bourson A, et al. Effects of rimonabant, a cannabinoid CB1 receptor ligand, on energy expenditure in lean rats. International Journal of Obesity. 2008 May;32(5):863–870
  27. Mailleux P, Vanderhaeghen JJ. Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry. Neuroscience. 1992;48(3):655–668
  28. Mackie K. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handbook of Experimental Pharmacology. 2005;(168):299–325
  29. Jelsing J, Larsen PJ, Vrang N. Identification of cannabinoid type 1 receptor expressing cocaine amphetamine-regulated transcript neurons in the rat hypothalamus and brainstem using in situ hybridization and immunohistochemistry. Neuroscience. 2008 Jun 23;154(2):641–652
  30. Wittmann G, Deli L, Kallo I, et al. Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus. The Journal of Comparative Neurology. 2007 Jul 10;503(2):270–279
  31. Schlicker E, Kathmann M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends in Pharmacological Sciences. 2001 Nov;22(11):565–572
  32. Di Marzo V. Targeting the endocannabinoid system: to enhance or reduce?. Nature Reviews. Drug Discovery. 2008 May;7(5):438–455
  33. Breivogel CS, Childers SR. The functional neuroanatomy of brain cannabinoid receptors. Neurobiology of Disease. 1998 Dec;5(6 Pt B):417–431
  34. Croci T, Manara L, Aureggi G, et al. In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum. British Journal of Pharmacology. 1998 Dec;125(7):1393–1395
  35. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992 Dec 18;258(5090):1946–1949
  36. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology. 1995 Jun 29;50(1):83–90
  37. Hanus L, Abu-Lafi S, Fride E, et al. 2-arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proceedings of the National Academy of Sciences of the United States of America. 2001 Mar 27;98(7):3662–3665
  38. Porter AC, Sauer JM, Knierman MD, et al. Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. The Journal of Pharmacology and Experimental Therapeutics. 2002 Jun;301(3):1020–1024
  39. Bisogno T, Melck D, Bobrov M, et al. N-acyl-dopamines: novel synthetic CB(1) cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochemical Journal. 2000 Nov 1;3:817–824351 Pt
  40. Elmquist JK, Coppari R, Balthasar N, et al. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. The Journal of Comparative Neurology. 2005 Dec 5;493(1):63–71
  41. Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. Nature. 2000 Apr 6;404(6778):661–671
  42. Jobst EE, Enriori PJ, Cowley MA. The electrophysiology of feeding circuits. Trends in Endocrinology and Metabolism. 2004 Dec;15(10):488–499
  43. Williams G, Bing C, Cai XJ, et al. The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiology & Behavior. 2001 Nov-Dec;74(4-5):683–701
  44. Adan RA, Tiesjema B, Hillebrand JJ, et al. The MC4 receptor and control of appetite. British Journal of Pharmacology. 2006 Dec;149(7):815–827
  45. Coppola A, Diano S. Hormonal regulation of the arcuate nucleus melanocortin system. Frontiers in Bioscience. 2007;12:3519–3530
  46. Ellacott KL, Cone RD. The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models. Philosophical Transactions of the Royal Society of London B Biological Sciences. 2006 Jul 29;361(1471):1265–1274
  47. Luquet S, Perez FA, Hnasko TS, et al. NPY/AgRP neurons are essential for feeding in adult mice but can be ablated in neonates. Science. 2005 Oct 28;310(5748):683–685
  48. Shutter JR, Graham M, Kinsey AC, et al. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes & Development. 1997 Mar 1;11(5):593–602
  49. Stanley BG, Leibowitz SF. Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior. Proceedings of the National Academy of Sciences of the United States of America. 1985 Jun;82(11):3940–3943
  50. Gropp E, Shanabrough M, Borok E, et al. Agouti-related peptide-expressing neurons are mandatory for feeding. Nature Neuroscience. 2005 Oct;8(10):1289–1291
  51. Cone RD. Studies on the physiological functions of the melanocortin system. Endocrine Reviews. 2006 Dec;27(7):736–749
  52. Butler AA. The melanocortin system and energy balance. Peptides. 2006 Feb;27(2):281–290
  53. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997 Jan 10;88(1):131–141
  54. Farooqi S, O'Rahilly S. Genetics of obesity in humans. Endocrine Reviews. 2006 Dec;27(7):710–718
  55. Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005 Nov 4;123(3):493–505
  56. Song CK, Vaughan CH, Keen-Rhinehart E, et al. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2008 Aug;295(2):R417–R428
  57. Richard D. Energy expenditure: a critical determinant of energy balance with key hypothalamic controls. Minerva Endocrinologica. 2007 Sep;32(3):173–183
  58. Kishi T, Aschkenasi CJ, Choi BJ, et al. Neuropeptide Y Y1 receptor mRNA in rodent brain: distribution and colocalization with melanocortin-4 receptor. The Journal of Comparative Neurology. 2005 Feb 14;482(3):217–243
  59. Morin SM, Gehlert DR. Distribution of NPY Y5-like immunoreactivity in the rat brain. Journal of Molecular Neuroscience. 2006;29(2):109–114
  60. Levine AS, Jewett DC, Cleary JP, et al. Our journey with neuropeptide Y: effects on ingestive behaviors and energy expenditure. Peptides. 2004 Mar;25(3):505–510
  61. Wilding JP, Gilbey SG, Bailey CJ, et al. Increased neuropeptide-Y messenger ribonucleic acid (mRNA) and decreased neurotensin mRNA in the hypothalamus of the obese (ob/ob) mouse. Endocrinology. 1993 May;132(5):1939–1944
  62. Sanacora G, Kershaw M, Finkelstein JA, et al. Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation. Endocrinology. 1990 Aug;127(2):730–737
  63. Wenger T, Ledent C, Tramu G. The endogenous cannabinoid, anandamide, activates the hypothalamo-pituitary-adrenal axis in CB1 cannabinoid receptor knockout mice. Neuroendocrinology. 2003 Dec;78(6):294–300
  64. Soria-Gomez E, Matias I, Rueda-Orozco PE, et al. Pharmacological enhancement of the endocannabinoid system in the nucleus accumbens shell stimulates food intake and increases c-Fos expression in the hypothalamus. British Journal of Pharmacology. 2007 Aug;151(7):1109–1116
  65. Allen KV, McGregor IS, Hunt GE, et al. Regional differences in naloxone modulation of Delta(9)-THC induced Fos expression in rat brain. Neuropharmacology. 2003 Feb;44(2):264–274
  66. Sinnayah P, Jobst EE, Rathner JA, et al. Feeding induced by cannabinoids is mediated independently of the melanocortin system. PLoS ONE. 2008;3(5):e2202
  67. Gamber KM, Macarthur H, Westfall TC. Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus. Neuropharmacology. 2005 Oct;49(5):646–652
  68. Verty AN, McGregor IS, Mallet PE. Paraventricular hypothalamic CB(1) cannabinoid receptors are involved in the feeding stimulatory effects of Delta(9)-tetrahydrocannabinol. Neuropharmacology. 2005 Dec;49(8):1101–1109
  69. Swanson LW, Sawchenko PE. Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annual Review of Neuroscience. 1983;6:269–324
  70. Loewy AD. Forebrain nuclei involved in autonomic control. Progress in Brain Research. 1991;87:253–268
  71. Thompson RH, Swanson LW. Structural characterization of a hypothalamic visceromotor pattern generator network. Brain Research. Brain Research Reviews. 2003 Mar;41(2-3):153–202
  72. Sawchenko PE. Toward a new neurobiology of energy balance, appetite, and obesity: the anatomists weigh in. The Journal of Comparative Neurology. 1998 Dec 28;402(4):435–441
  73. Hosoya Y, Matsukawa , Okado N, et al. Oxytocinergic innervation to the upper thoracic sympathetic preganglionic neurons in the rat. A light and electron microscopical study using a combined retrograde transport and immunocytochemical technique. Experimental Brain Research. 1995;107(1):9–16
  74. Kishi T, Aschkenasi CJ, Lee CE, et al. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. The Journal of Comparative Neurology. 2003 Mar 10;457(3):213–235
  75. Kublaoui BM, Gemelli T, Tolson KP, et al. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Molecular Endocrinology. 2008 Jul;22(7):1723–1734
  76. Oldfield BJ, Giles ME, Watson A, et al. The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience. 2002;110(3):515–526
  77. Voss-Andreae A, Murphy JG, Ellacott KL, et al. Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology. 2007 Apr;148(4):1550–1560
  78. Verty AN, McFarlane JR, McGregor IS, et al. Evidence for an interaction between CB1 cannabinoid and melanocortin MCR-4 receptors in regulating food intake. Endocrinology. 2004 Jul;145(7):3224–3231
  79. Kola B, Farkas I, Christ-Crain M, et al. The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PLoS ONE. 2008;3(3):e1797
  80. Tucci SA, Rogers EK, Korbonits M, et al. The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. British Journal of Pharmacology. 2004 Nov;143(5):520–523
  81. Veiga M, Bloise F, Costa ESR et al. Acute Effects of Endocannabinoid Anandamide and CB-1 receptor antagonist, AM251 in the Regulation of Thyrotropin Secretion. The Journal of Endocrinology, in press.
  82. Cota D. The role of the endocannabinoid system in the regulation of hypothalamic-pituitary-adrenal axis activity. Journal of Neuroendocrinology. 2008 May;20(Suppl. 1):35–38
  83. Chrousos GP, Gold PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA: The Journal of the American Medical Association. 1992 Mar 4;267(9):1244–1252
  84. Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale Journal of Biology and Medicine. 1951 Nov;24(2):123–140
  85. Berthoud HR. Homeostatic and non-homeostatic pathways involved in the control of food intake and energy balance. Obesity (Silver Spring). 2006 Aug;14(Suppl. 5):197S–200S
  86. Morrison SF. Central pathways controlling brown adipose tissue thermogenesis. News in Physiological Sciences. 2004 Apr;19:67–74
  87. Cerri M, Morrison SF. Activation of lateral hypothalamic neurons stimulates brown adipose tissue thermogenesis. Neuroscience. 2005;135(2):627–638
  88. Zheng H, Patterson LM, Morrison C, et al. Melanin concentrating hormone innervation of caudal brainstem areas involved in gastrointestinal functions and energy balance. Neuroscience. 2005;135(2):611–625
  89. Nahon JL. The melanocortins and melanin-concentrating hormone in the central regulation of feeding behavior and energy homeostasis. Comptes Rendus Biologies. 2006 Aug;329(8):623–638[Discussion 53–55]
  90. Pissios P, Bradley RL, Maratos-Flier E. Expanding the scales: The multiple roles of MCH in regulating energy balance and other biological functions. Endocrine Reviews. 2006 Oct;27(6):606–620
  91. Gomori A, Ishihara A, Ito M, et al. Chronic intracerebroventricular infusion of MCH causes obesity in mice. Melanin-concentrating hormone. American Journal of Physiology. Endocrinology and Metabolism. 2003 Mar;284(3):E583–E588
  92. Ludwig DS, Tritos NA, Mastaitis JW, et al. Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. The Journal of Clinical Investigation. 2001 Feb;107(3):379–386
  93. Shearman LP, Camacho RE, Sloan Stribling D, et al. Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. European Journal of Pharmacology. 2003 Aug 15;475(1-3):37–47
  94. Shimada M, Tritos NA, Lowell BB, et al. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998 Dec 17;396(6712):670–674
  95. Alon T, Friedman JM. Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons. The Journal of Neuroscience. 2006 Jan 11;26(2):389–397
  96. Chen Y, Hu C, Hsu CK, et al. Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity. Endocrinology. 2002 Jul;143(7):2469–2477
  97. Marsh DJ, Weingarth DT, Novi DE, et al. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proceedings of the National Academy of Sciences of the United States of America. 2002 Mar 5;99(5):3240–3245
  98. Jo YH, Chen YJ, Chua SC, et al. Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Neuron. 2005 Dec 22;48(6):1055–1066
  99. Cvetkovic V, Brischoux F, Jacquemard C, et al. Characterization of subpopulations of neurons producing melanin-concentrating hormone in the rat ventral diencephalon. Journal of Neurochemistry. 2004 Nov;91(4):911–919
  100. Kelley AE, Baldo BA, Pratt WE. A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward. The Journal of Comparative Neurology. 2005 Dec 5;493(1):72–85
  101. Saito Y, Cheng M, Leslie FM, et al. Expression of the melanin-concentrating hormone (MCH) receptor mRNA in the rat brain. The Journal of Comparative Neurology. 2001 Jun 18;435(1):26–40
  102. Cano G, Passerin AM, Schiltz JC, et al. Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure. The Journal of Comparative Neurology. 2003 Jun 2;460(3):303–326
  103. Hervieu GJ, Cluderay JE, Harrison D, et al. The distribution of the mRNA and protein products of the melanin-concentrating hormone (MCH) receptor gene, slc-1, in the central nervous system of the rat. European Journal of Neuroscience. 2000 Apr;12(4):1194–1216
  104. Mahler SV, Smith KS, Berridge KC. Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances ‘liking’ of a sweet reward. Neuropsychopharmacology. 2007 Nov;32(11):2267–2278
  105. Georgescu D, Sears RM, Hommel JD, et al. The hypothalamic neuropeptide melanin-concentrating hormone acts in the nucleus accumbens to modulate feeding behavior and forced-swim performance. The Journal of Neuroscience. 2005 Mar 16;25(11):2933–2940
  106. Yang SC, Shieh KR, Li HY. Cocaine- and amphetamine-regulated transcript in the nucleus accumbens participates in the regulation of feeding behavior in rats. Neuroscience. 2005;133(3):841–851
  107. Osei-Hyiaman D, Depetrillo M, Harvey-White J, et al. Cocaine- and amphetamine-related transcript is involved in the orexigenic effect of endogenous anandamide. Neuroendocrinology. 2005;81(4):273–282
  108. Segal-Lieberman G, Bradley RL, Kokkotou E, et al. Melanin-concentrating hormone is a critical mediator of the leptin-deficient phenotype. Proceedings of the National Academy of Sciences of the United States of America. 2003 Aug 19;100(17):10085–10090
  109. Kokkotou E, Jeon JY, Wang X, et al. Mice with MCH ablation resist diet-induced obesity through strain-specific mechanisms. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2005 Jul;289(1):R117–R124
  110. Swanson LW, Sanchez-Watts G, Watts AG. Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone. Neuroscience Letters. 2005 Oct 21;387(2):80–84
  111. Date Y, Ueta Y, Yamashita H, et al. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proceedings of the National Academy of Sciences of the United States of America. 1999 Jan 19;96(2):748–753
  112. Peyron C, Tighe DK, van den Pol AN, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. The Journal of Neuroscience. 1998 Dec 1;18(23):9996–10015
  113. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998 Feb 20;92(4):573–585
  114. Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature. 2005 Sep 22;437(7058):556–559
  115. Yoshimichi G, Yoshimatsu H, Masaki T, et al. Orexin-A regulates body temperature in coordination with arousal status. Experimental Biology and Medicine (Maywood). 2001 May;226(5):468–476
  116. Yasuda T, Masaki T, Kakuma T, et al. Dual regulatory effects of orexins on sympathetic nerve activity innervating brown adipose tissue in rats. Endocrinology. 2005 Jun;146(6):2744–2748
  117. Kotz CM. Integration of feeding and spontaneous physical activity: role for orexin. Physiology & Behavior. 2006 Jun 30;88(3):294–301
  118. Hara J, Beuckmann CT, Nambu T, et al. Genetic ablation of orexin neurons in mice results in narcolepsy, hypophagia, and obesity. Neuron. 2001 May;30(2):345–354
  119. Huang H, Acuna-Goycolea C, Li Y, et al. Cannabinoids excite hypothalamic melanin-concentrating hormone but inhibit hypocretin/orexin neurons: implications for cannabinoid actions on food intake and cognitive arousal. The Journal of Neuroscience. 2007 May 2;27(18):4870–4881
  120. Sakurai T. Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Medicine Reviews. 2005 Aug;9(4):231–241
  121. Jamshidi N, Taylor DA. Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. British Journal of Pharmacology. 2001 Nov;134(6):1151–1154
  122. Elias CF, Lee C, Kelly J, et al. Leptin activates hypothalamic CART neurons projecting to the spinal cord. Neuron. 1998 Dec;21(6):1375–1385
  123. Vrang N. Anatomy of hypothalamic CART neurons. Peptides. 2006 Aug;27(8):1970–1980
  124. Grill HJ, Kaplan JM. Interoceptive and integrative contributions of forebrain and brainstem to energy balance control. International Journal of Obesity and Related Metabolic Disorders. 2001 Dec;25(Suppl. 5):S73–S77
  125. Grill HJ. Distributed neural control of energy balance: contributions from hindbrain and hypothalamus. Obesity (Silver Spring). 2006 Aug;14(Suppl. 5):216S–221S
  126. Harris RB, Bartness TJ, Grill HJ. Leptin responsiveness in chronically decerebrate rats. Endocrinology. 2007 Oct;148(10):4623–4633
  127. Williams DL, Kaplan JM, Grill HJ. The role of the dorsal vagal complex and the vagus nerve in feeding effects of melanocortin-3/4 receptor stimulation. Endocrinology. 2000 Apr;141(4):1332–1337
  128. Faulconbridge LF, Grill HJ, Kaplan JM. Distinct forebrain and caudal brainstem contributions to the neuropeptide Y mediation of ghrelin hyperphagia. Diabetes. 2005 Jul;54(7):1985–1993
  129. Bamshad M, Song CK, Bartness TJ. CNS origins of the sympathetic nervous system outflow to brown adipose tissue. American Journal of Physiology. 1999 Jun;276(6 Pt 2):R1569–R1578
  130. Oldfield BJ, Allen AM, Davern P, et al. Lateral hypothalamic ‘command neurons’ with axonal projections to regions involved in both feeding and thermogenesis. European Journal of Neuroscience. 2007 Apr;25(8):2404–2412
  131. Moran TH. Gut peptides in the control of food intake: 30 years of ideas. Physiology & Behavior. 2004 Aug;82(1):175–180
  132. Moran TH. Gut peptide signaling in the controls of food intake. Obesity (Silver Spring). 2006 Aug;14(Suppl. 5):250S–253S
  133. Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006 Dec 14;444(7121):854–859
  134. Cummings DE, Overduin J. Gastrointestinal regulation of food intake. The Journal of Clinical Investigation. 2007 Jan;117(1):13–23
  135. Burdyga G, Lal S, Varro A, et al. Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. The Journal of Neuroscience. 2004 Mar 17;24(11):2708–2715
  136. Burdyga G, Varro A, Dimaline R, et al. Ghrelin receptors in rat and human nodose ganglia: putative role in regulating CB-1 and MCH receptor abundance. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2006 Jun;290(6):G1289–G1297
  137. Herkenham M, Lynn AB, Little MD, et al. Cannabinoid receptor localization in brain. Proceedings of the National Academy of Sciences of the United States of America. 1990 Mar;87(5):1932–1936
  138. Chin CL, Tovcimak AE, Hradil VP, et al. Differential effects of cannabinoid receptor agonists on regional brain activity using pharmacological MRI. British Journal of Pharmacology. 2008 Jan;153(2):367–379
  139. Burns HD, Van Laere K, Sanabria-Bohorquez S, et al. [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proceedings of the National Academy of Sciences of the United States of America. 2007 Jun 5;104(23):9800–9805
  140. Addy C, Wright H, Van Laere K, et al. The acyclic CB1R inverse agonist taranabant mediates weight loss by increasing energy expenditure and decreasing caloric intake. Cell Metabolism. 2008 Jan;7(1):68–78
  141. Salamone JD. The involvement of nucleus accumbens dopamine in appetitive and aversive motivation. Behavioural Brain Research. 1994 Apr 18;61(2):117–133
  142. Heimer L, Alheid GF, de Olmos JS, et al. The accumbens: beyond the core-shell dichotomy. The Journal of Neuropsychiatry and Clinical Neurosciences. 1997 Summer;9(3):354–381
  143. Berridge KC, Robinson TE. Parsing reward. Trends in Neurosciences. 2003 Sep;26(9):507–513
  144. Finlayson G, King N, Blundell JE. Liking vs. wanting food: importance for human appetite control and weight regulation. Neuroscience & Biobehavioral Reviews. 2007;31(7):987–1002
  145. Pecina S, Cagniard B, Berridge KC, et al. Hyperdopaminergic mutant mice have higher ‘wanting’ but not ‘liking’ for sweet rewards. The Journal of Neuroscience. 2003 Oct 15;23(28):9395–9402
  146. Pecina S, Smith KS, Berridge KC. Hedonic hot spots in the brain. Neuroscientist. 2006 Dec;12(6):500–511
  147. Pecina S, Berridge KC. Hedonic hot spot in nucleus accumbens shell: where do mu-opioids cause increased hedonic impact of sweetness?. The Journal of Neuroscience. 2005 Dec 14;25(50):11777–11786
  148. Fusco FR, Martorana A, Giampa C, et al. Immunolocalization of CB1 receptor in rat striatal neurons: a confocal microscopy study. Synapse (New York, N.Y.). 2004 Sep 1;53(3):159–167
  149. Matyas F, Yanovsky Y, Mackie K, et al. Subcellular localization of type 1 cannabinoid receptors in the rat basal ganglia. Neuroscience. 2006;137(1):337–361
  150. Robledo P, Berrendero F, Ozaita A, et al. Advances in the field of cannabinoid–opioid cross-talk. Addiction Biology. 2008 Jun;13(2):213–224
  151. Fattore L, Cossu G, Spano MS, et al. Cannabinoids and reward: interactions with the opioid system. Critical Review Neurobiology. 2004;16(1-2):147–158
  152. Bjursell M, Gerdin AK, Lelliott CJ, et al. Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice. American Journal of Physiology. Endocrinology and Metabolism. 2008 Feb;294(2):E251–E260
  153. Moreira FA, Lutz B. The endocannabinoid system: emotion, learning and addiction. Addiction Biology. 2008 Jun;13(2):196–212
  154. de Fonseca FR, Schneider M. The endogenous cannabinoid system and drug addiction: 20 years after the discovery of the CB1 receptor. Addiction Biology. 2008 Jun;13(2):143–146
  155. Matyas F, Urban GM, Watanabe M, et al. Identification of the sites of 2-arachidonoylglycerol synthesis and action imply retrograde endocannabinoid signaling at both GABAergic and glutamatergic synapses in the ventral tegmental area. Neuropharmacology. 2008 Jan;54(1):95–107
  156. Koch JE. Delta(9)-THC stimulates food intake in Lewis rats: effects on chow, high-fat and sweet high-fat diets. Pharmacology Biochemistry and Behavior. 2001 Mar;68(3):539–543
  157. Williams CM, Kirkham TC. Observational analysis of feeding induced by Delta9-THC and anandamide. Physiology & Behavior. 2002 Jun 1;76(2):241–250
  158. Chaperon F, Soubrie P, Puech AJ, et al. Involvement of central cannabinoid (CB1) receptors in the establishment of place conditioning in rats. Psychopharmacology. 1998 Feb;135(4):324–332
  159. Maccioni P, Pes D, Carai MA, et al. Suppression by the cannabinoid CB1 receptor antagonist, rimonabant, of the reinforcing and motivational properties of a chocolate-flavoured beverage in rats. Behavioural Pharmacology. 2008 May;19(3):197–209
  160. Scheen AJ, Finer N, Hollander P, et al. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study. Lancet. 2006 Nov 11;368(9548):1660–1672
  161. Thornton-Jones ZD, Vickers SP, Clifton PG. The cannabinoid CB1 receptor antagonist SR141716A reduces appetitive and consummatory responses for food. Psychopharmacology. 2005 May;179(2):452–460
  162. Melis T, Succu S, Sanna F, et al. The cannabinoid antagonist SR 141716A (Rimonabant) reduces the increase of extra-cellular dopamine release in the rat nucleus accumbens induced by a novel high palatable food. Neuroscience Letters. 2007 Jun 4;419(3):231–235

PII: S1521-690X(08)00140-1

doi: 10.1016/j.beem.2008.10.007

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 1 , Pages 17-32 , February 2009