Appetite and Metabolic Effects of Ghrelin and Cannabinoids: Involvement of AMP-Activated Protein Kinase

Vitamins and Hormones

Volumn 77, Issue , 2007, Pages 121-148

  Thuijl, Hinke van ^a   Kola, Blerina ^a   Korbonits, Márta ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMP ACTIVATED PROTEIN KINASES; AMP-ACTIVATED PROTEIN KINASES; CANNABINOID; GHRELIN; MULTIENZYME COMPLEX; PROTEIN SERINE THREONINE KINASE; UNCLASSIFIED DRUG;

ANIMAL; APPETITE; DRUG EFFECT; ENERGY METABOLISM; HUMAN; METABOLISM; MOUSE; PHYSIOLOGY; RAT; REVIEW;

ANIMALS; APPETITE; CANNABINOIDS; ENERGY METABOLISM; GHRELIN; HUMANS; MICE; MULTIENZYME COMPLEXES; PROTEIN-SERINE-THREONINE KINASES; RATS;

EID: 35648999478     PISSN: 00836729     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0083-6729(06)77006-6     Document Type: Review

References (159)

1. Addolorato G., Capristo E., Leggio L., Ferrulli A., Abenavoli L., Malandrino N., Farnetti S., Domenicali M., D'Angelo C., Vonghia L., Mirijello A., Cardone S., et al. Relationship between ghrelin levels, alcohol craving, and nutritional status in current alcoholic patients. Alcohol Clin. Exp. Res. 30 (2006) 1933-1937
2. Altarejos J.Y., Taniguchi M., Clanachan A.S., and Lopaschuk G.D. Myocardial ischemia differentially regulates LKB1 and an alternate 5′-AMP-activated protein kinase kinase. J. Biol. Chem. 280 (2005) 183-190
3. Arad M., Benson D.W., Perez-Atayde A.R., McKenna W.J., Sparks E.A., Kanter R.J., McGarry K., Seidman J.G., and Seidman C.E. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J. Clin. Invest. 109 (2002) 357-362
4. Ariyasu H., Takaya K., Tagami T., Ogawa Y., Hosoda K., Akamizu T., Suda M., Koh T., Natsui K., Toyooka S., Shirakami G., Usui T., et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J. Clin. Endocrinol. Metab. 86 (2001) 4753-4758
5. Arnold M., Mura A., Langhans W., and Geary N. Gut vagal afferents are not necessary for the eating-stimulatory effect of intraperitoneally injected ghrelin in the rat. J. Neurosci. 26 (2006) 11052-11060
6. Arnone M., Maruani J., Chaperon F., Thiebot M.H., Poncelet M., Soubrie P., and Le Fur G. Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors. Psychopharmacology (Berl.) 132 (1997) 104-106
7. Asakawa A., Inui A., Kaga T., Yuzuriha H., Nagata T., Ueno N., Makino S., Fujimiya M., Niijima A., Fujino M.A., and Kasuga M. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120 (2001) 337-345
8. Asakawa A., Inui A., Kaga T., Katsuura G., Fujimiya M., Fujino M.A., and Kasuga M. Antagonism of ghrelin receptor reduces food intake and body weight gain in mice. Gut 52 (2003) 947-952
9. Avraham Y., Ben Shushan D., Breuer A., Zolotarev O., Okon A., Fink N., Katz V., and Berry E.M. Very low doses of delta 8-THC increase food consumption and alter neurotransmitter levels following weight loss. Pharmacol. Biochem. Behav. 77 (2004) 675-684
10. Bagnasco M., Tulipano G., Melis M.R., Argiolas A., Cocchi D., and Muller E.E. Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. Regul. Pept. 111 (2003) 161-167
11. Baldanzi G., Filigheddu N., Cutrupi S., Catapano F., Bonissoni S., Fubini A., Malan D., Baj G., Granata R., Broglio F., Papotti M., Surico N., et al. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyocytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT. J. Cell Biol. 159 (2002) 1029-1037
12. Barazzoni R., Bosutti A., Stebel M., Cattin M.R., Roder E., Visintin L., Cattin L., Biolo G., Zanetti M., and Guarnieri G. Ghrelin regulates mitochondrial-lipid metabolism gene expression and tissue fat distribution in liver and skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 288 (2005) E228-E235
13. Bensaid M., Gary-Bobo M., Esclangon A., Maffrand J.P., Le Fur G., Oury-Donat F., and Soubrie P. 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 (2003) 908-914
14. Bertoli S., Magni P., Krogh V., Ruscica M., Dozio E., Testolin G., and Battezzati A. Is ghrelin a signal of decreased fat-free mass in elderly subjects?. Eur. J. Endocrinol. 155 (2006) 321-330
15. Bodart V., Febbraio M., Demers A., McNicoll N., Pohankova P., Perreault A., Sejlitz T., Escher E., Silverstein R.L., Lamontagne D., and Ong H. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circ. Res. 90 (2002) 844-849
16. Broglio F., Benso A., Valetto M.R., Gottero C., Quaranta L., Podio V., Arvat E., Bobbio M., Bisi G., and Ghigo E. Growth hormone-independent cardiotropic activities of growth hormone- releasing peptides in normal subjects, in patients with growth hormone deficiency, and in patients with idiopathic or ischemic dilated cardiomyopathy. Endocrine 14 (2001) 105-108
17. Broglio F., Benso A., Castiglioni C., Gottero C., Prodam F., Destefanis S., Gauna C., van der Lely A.J., Deghenghi R., Bo M., Arvat E., and Ghigo E. The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects. J. Clin. Endocrinol. Metab. 88 (2003) 1537-1542
18. Brown M.S., and Goldstein J.L. Sterol regulatory element binding proteins (SREBPs): Controllers of lipid synthesis and cellular uptake. Nutr. Rev. 56 (1998) S1-S3
19. Brown L.M., Benoit S.C., Woods S.C., and Clegg D.J. Intraventricular (i3vt) ghrelin increases food intake in fatty Zucker rats. Peptides 28 (2007) 612-616
20. Callahan H.S., Cummings D.E., Pepe M.S., Breen P.A., Matthys C.C., and Weigle D.S. Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal interval in humans. J. Clin. Endocrinol. Metab. 89 (2004) 1319-1324
21. Cenni G., Blandina P., Mackie K., Nosi D., Formigli L., Giannoni P., Ballini C., Della C.L., Francesco M.P., and Beatrice P.M. Differential effect of cannabinoid agonists and endocannabinoids on histamine release from distinct regions of the rat brain. Eur. J. Neurosci. 24 (2006) 1633-1644
22. Chan J.L., Bullen J., Lee J.H., Yiannakouris N., and Mantzoros C.S. Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects. J. Clin. Endocrinol. Metab. 89 (2004) 335-343
23. Chang L., Ren Y., Liu X., Li W.G., Yang J., Geng B., Weintraub N.L., and Tang C. Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. J. Cardiovasc. Pharmacol. 43 (2004) 165-170
24. Choi K., Roh S.G., Hong Y.H., Shrestha Y.B., Hishikawa D., Chen C., Kojima M., Kangawa K., and Sasaki S. The role of ghrelin and growth hormone secretagogues receptor on rat adipogenesis. Endocrinology 144 (2003) 754-759
25. Cota D., Marsicano G., Tschop M., Grubler Y., Flachskamm C., Schubert M., Auer D., Yassouridis A., Thone-Reineke C., Ortmann S., Tomassoni F., Cervino C., et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J. Clin. Invest. 112 (2003) 423-431
26. Cote M., Matias I., Lemieux I., Petrosino S., Almeras N., Despres J.P., and Di Marzo V. Circulating endocannabinoid levels, abdominal adiposity and related cardiometabolic risk factors in obese men. Int. J. Obes. (Lond.) 31 4 (2007) 692-699
27. Couce M.E., Cottam D., Esplen J., Teijeiro R., Schauer P., and Burguera B. Potential role of hypothalamic ghrelin in the pathogenesis of human obesity. J. Endocrinol. Invest. 29 (2006) 599-605
28. Crute B.E., Seefeld K., Gamble J., Kemp B.E., and Witters L.A. Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase. J. Biol. Chem. 273 (1998) 35347-35354
29. Cummings D.E. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol. Behav. 89 (2006) 71-84
30. Cummings D.E., and Shannon M.H. Roles for ghrelin in the regulation of appetite and body weight. Arch. Surg. 138 (2003) 389-396
31. Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., and Weigle D.S. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50 (2001) 1714-1719
32. Cummings D.E., Frayo R.S., Marmonier C., Aubert R., and Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am. J. Physiol. Endocrinol. Metab. 287 (2004) E297-E304
33. Date Y., Murakami N., Toshinai K., Matsukura S., Niijima A., Matsuo H., Kangawa K., and Nakazato M. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology 123 (2002) 1120-1128
34. Daval M., Foufelle F., and Ferre P. Functions of AMP-activated protein kinase in adipose tissue. J. Physiol. 574 (2006) 55-62
35. Davies S.P., Helps N.R., Cohen P.T., and Hardie D.G. 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett. 377 (1995) 421-425
36. Davis K.W., Wellman P.J., and Clifford P.S. Augmented cocaine conditioned place preference in rats pretreated with systemic ghrelin. Regul. Pept. 140 3 (2007) 148-152
37. De Vriese C., Hacquebard M., Gregoire F., Carpentier Y., and Delporte C. Ghrelin interacts with human plasma lipoproteins. Endocrinology 148 5 (2007) 2355-2362
38. Demers A., McNicoll N., Febbraio M., Servant M., Marleau S., Silverstein R., and Ong H. Identification of the growth hormone-releasing peptide binding site in CD36: A photoaffinity cross-linking study. Biochem. J. 382 (2004) 417-424
39. Despres J.P., Golay A., and Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Eng. J. Med. 353 (2005) 2121-2134
40. Devane W.A., Hanus L., Breuer A., Pertwee R.G., Stevenson L.A., Griffin G., Gibson D., Mandelbaum A., Etinger A., and Mechoulam R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258 (1992) 1946-1949
41. Di Marzo V., Goparaju S.K., Wang L., Liu J., Batkai S., Jarai Z., Fezza F., Miura G.I., Palmiter R.D., Sugiura T., and Kunos G. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 410 (2001) 822-825
42. Di Marzo V., and Matias L. Endocannabinoid control of food intake and energy balance. Nat. Neurosci. 8 (2005) 585-589
43. Diraison F., Yankah V., Letexier D., Dusserre E., Jones P., and Beylot M. Differences in the regulation of adipose tissue and liver lipogenesis by carbohydrates in humans. J. Lipid Res. 44 (2003) 846-853
44. Dyck J.R., and Lopaschuk G.D. Malonyl CoA control of fatty acid oxidation in the ischemic heart. J. Mol. Cell. Cardiol. 34 (2002) 1099-1109
45. Engeli S., Bohnke J., Feldpausch M., Gorzelniak K., Janke J., Batkai S., Pacher P., Harvey-White J., Luft F.C., Sharma A.M., and Jordan J. Activation of the peripheral endocannabinoid system in human obesity. Diabetes 54 (2005) 2838-2843
46. English P.J., Ghatei M.A., Malik I.A., Bloom S.R., and Wilding J.P. Food fails to suppress ghrelin levels in obese humans. J. Clin. Endocrinol. Metab. 87 (2002) 2984-2987
47. Faulconbridge L.F., Cummings D.E., Kaplan J.M., and Grill H.J. Hyperphagic effects of brainstem ghrelin administration. Diabetes 52 (2003) 2260-2265
48. Foretz M., Ancellin N., Andreelli F., Saintillan Y., Grondin P., Kahn A., Thorens B., Vaulont S., and Viollet B. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 54 (2005) 1331-1339
49. Foster-Schubert K.E., McTiernan A., Frayo R.S., Schwartz R.S., Rajan K.B., Yasui Y., Tworoger S.S., and Cummings D.E. Human plasma ghrelin levels increase during a one-year exercise program. J. Clin. Endocrinol. Metab. 90 (2005) 820-825
50. Frascarelli S., Ghelardoni S., Ronca-Testoni S., and Zucchi R. Effect of ghrelin and synthetic growth hormone secretagogues in normal and ischemic rat heart. Basic Res. Cardiol. 98 (2003) 401-405
51. Fryer L.G., and Carling D. AMP-activated protein kinase and the metabolic syndrome. Biochem. Soc. Trans. 33 (2005) 362-366
52. Gallate J.E., and McGregor I.S. The motivation for beer in rats: Effects of ritanserin, naloxone and SR 141716. Psychopharmacology (Ber.) 142 (1999) 302-308
53. Gallate J.E., Saharov T., Mallet P.E., and McGregor I.S. Increased motivation for beer in rats following administration of a cannabinoid CB1 receptor agonist. Eur. J. Pharmacol. 370 (1999) 233-240
54. Garcia J.M., Iyer D., Poston W.S., Marcelli M., Reeves R., Foreyt J., and Balasubramanyam A. Rise of plasma ghrelin with weight loss is not sustained during weight maintenance. Obesity (Silver Spring) 14 (2006) 1716-1723
55. Gauna C., Delhantyz P.J., Hofland L.J., Janssen J.A., Broglio F., Ross R.J., Ghigo E., and van der Lely A.J. Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes. J. Clin. Endocrinol. Metab. 90 (2005) 1055-1060
56. Gil-Campos M., Aguilera C.M., Canete R., and Gil A. Ghrelin: A hormone regulating food intake and energy homeostasis. Br. J. Nutr. 96 (2006) 201-226
57. Goldstone A.P., Thomas E.L., Brynes A.E., Castroman G., Edwards R., Ghatei M.A., Frost G., Holland A.J., Grossman A.B., Korbonits M., Bloom S.R., and Bell J.D. Elevated fasting plasma ghrelin in Prader-Willi syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance. J. Clin. Endocrinol. Metab. 89 (2004) 1718-1726
58. Hansen T.K., Dall R., Hosoda H., Kojima M., Kangawa K., Christiansen J.S., and Jorgensen J.O. Weight loss increases circulating levels of ghrelin in human obesity. Clin. Endocrinol. (Oxf.) 56 (2002) 203-206
59. Hardie D.G. The AMP-activated protein kinase pathway-new players upstream and downstream. J. Cell Sci. 117 (2004) 5479-5487
60. Hardie D.G., and Hawley S.A. AMP-activated protein kinase: The energy charge hypothesis revisited. Bioessays 23 (2001) 1112-1119
61. Hardie D.G., Salt I.P., Hawley S.A., and Davies S.P. AMP-activated protein kinase: An ultrasensitive system for monitoring cellular energy charge. Biochem. J. 338 Pt. 3 (1999) 717-722
62. Hawley S.A., Davison M., Woods A., Davies S.P., Beri R.K., Carling D., and Hardie D.G. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J. Biol. Chem. 271 (1996) 27879-27887
63. Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., Frenguelli B.G., and Hardie D.G. Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2 (2005) 9-19
64. Heijboer A.C., Pijl H., Van den Hoek A.M., Havekes L.M., Romijn J.A., and Corssmit E.P. Gut-brain axis: Regulation of glucose metabolism. J. Neuroendocrinol. 18 (2006) 883-894
65. Howlett A.C. The cannabinoid receptors. Prostaglandins Other Lipid Mediat. (2002) 68-69 619-631
66. 2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J. Biol. Chem. 280 (2005) 29060-29066
67. Iglesias M.J., Pineiro R., Blanco M., Gallego R., Dieguez C., Gualillo O., Gonzalez-Juanatey J.R., and Lago F. Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes. Cardiovasc. Res. 62 (2004) 481-488
68. Jamshidi N., and Taylor D.A. Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats. Br. J. Pharmacol. 134 (2001) 1151-1154
69. Katugampola S.D., Pallikaros Z., and Davenport A.P. [125I-His(9)]-ghrelin, a novel radioligand for localizing GHS orphan receptors in human and rat tissue: Up-regulation of receptors with athersclerosis. Br. J. Pharmacol. 134 (2001) 143-149
70. Kim E.K., Miller I., Aja S., Landree L.E., Pinn M., McFadden J., Kuhajda F.P., Moran T.H., and Ronnett G.V. C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase. J. Biol. Chem. 279 (2004) 19970-19976
71. Kim S.J., Nian C., and McIntosh C.H. Activation of lipoprotein lipase (LPL) by glucose-dependent insulinotropic polypeptide (GIP) in adipocytes: A role for a protein kinase B (PKB), LKB1 and AMP-activated protein kinase (AMPK) cascade. J. Biol. Chem. 282 (2007) 8557-8567
72. Kirkham T.C., Williams C.M., Fezza F., and 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. 136 (2002) 550-557
73. Koch J.E. Delta(9)-THC stimulates food intake in Lewis rats: Effects on chow, high-fat and sweet high-fat diets. Pharmacol. Biochem. Behav. 68 (2001) 539-543
74. Koh H.J., Hirshman M.F., He H., Li Y., Manabe Y., Balschi J.A., and Goodyear L.J. Epinephrine is a critical mediator of acute exercise-induced AMP-activated protein kinase activation in adipocytes. Biochem. J. 403(3) (2007) 473-481
75. Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., and Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402 (1999) 656-660
76. Kola B., Hubina E., Tucci S.A., Kirkham T.C., Garcia E.A., Mitchell S.E., Williams L.M., Hawley S.A., Hardie D.G., Grossman A.B., and Korbonits M. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J. Biol. Chem. 280 (2005) 25196-25201
77. Korbonits M., Goldstone A.P., Gueorguiev M., and Grossman A.B. Ghrelin-a hormone with multiple functions. Front. Neuroendocrinol. 25 (2004) 27-68
78. Korbonits M., Blaine D., Elia M., and Powell-Tuck J. Refeeding David Blaine-studies after a 44-day fast. N. Eng. J. Med. 353 (2005) 2306-2307
79. Krsek M., Rosicka M., Haluzik M., Svobodova J., Kotrlikova E., Justova V., Lacinova Z., and Jarkovska Z. Plasma ghrelin levels in patients with short bowel syndrome. Endocr. Res. 28 (2002) 27-33
80. Lagneux C., and Lamontagne D. Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide. Br. J. Pharmacol. 132 (2001) 793-796
81. Lee W.J., Koh E.H., Won J.C., Kim M.S., Park J.Y., and Lee K.U. Obesity: The role of hypothalamic AMP-activated protein kinase in body weight regulation. Int. J. Biochem. Cell Biol. 37 (2005) 2254-2259
82. Li H.L., Yin R., Chen D., Liu D., Wang D., Yang Q., and Dong Y.G. Long-term activation of adenosine monophosphate-activated protein kinase attenuates pressure-overload-induced cardiac hypertrophy. J. Cell Biochem. 100 (2007) 1086-1099
83. Locke W., Kirgis H.D., Bowers C.Y., and Abdoh A.A. Intracerebroventricular growth-hormone-releasing peptide-6 stimulates eating without affecting plasma growth hormone responses in rats. Life Sci. 56 (1995) 1347-1352
84. Marleau S., Harb D., Bujold K., Avallone R., Iken K., Wang Y., Demers A., Sirois M.G., Febbraio M., Silverstein R.L., Tremblay A., and Ong H. EP 80317, a ligand of the CD36 scavenger receptor, protects apolipoprotein E-deficient mice from developing atherosclerotic lesions. Faseb J. 19 (2005) 1869-1871
85. Marsin A.S., Bouzin C., Bertrand L., and Hue L. The stimulation of glycolysis by hypoxia in activated monocytes is mediated by AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase. J. Biol. Chem. 277 (2002) 30778-30783
86. Matias I., and Di Marzo V. Endocannabinoid synthesis and degradation, and their regulation in the framework of energy balance. J. Endocrinol. Invest. 29 (2006) 15-26
87. 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., 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. 91 (2006) 3171-3180
88. Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., and Bonner T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346 (1990) 561-564
89. Matsumura K., Tsuchihashi T., Fujii K., Abe I., and Iida M. Central ghrelin modulates sympathetic activity in conscious rabbits. Hypertension 40 (2002) 694-699
90. McCrimmon R.J., Fan X., Ding Y., Zhu W., Jacob R.J., and Sherwin R.S. Potential role for AMP-activated protein kinase in hypoglycemia sensing in the ventromedial hypothalamus. Diabetes 53 (2004) 1953-1958
91. Mechoulam R., Ben Shabat S., Hanus L., Ligumsky M., Kaminski N.E., Schatz A.R., Gopher A., Almog S., Martin B.R., Compton D.R., Pertwee R.G., Griffin G., et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50 (1995) 83-90
92. Minokoshi Y., Kim Y.B., Peroni O.D., Fryer L.G., Muller C., Carling D., and Kahn B.B. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 415 (2002) 339-343
93. Minokoshi Y., Alquier T., Furukawa N., Kim Y.B., Lee A., Xue B., Mu J., Foufelle F., Ferre P., Birnbaum M.J., Stuck B.J., and Kahn B.B. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428 (2004) 569-574
94. Monteleone P., Matias I., Martiadis V., De Petrocellis L., Maj M., and Di Marzo V. Blood levels of the endocannabinoid anandamide are increased in anorexia nervosa and in binge-eating disorder, but not in bulimia nervosa. Neuropsychopharmacology 30 (2005) 1216-1221
95. Muccioli G., Pons N., Ghe C., Catapano F., Granata R., and Ghigo E. Ghrelin and des-acyl ghrelin both inhibit isoproterenol-induced lipolysis in rat adipocytes via a non-type 1a growth hormone secretagogue receptor. Eur. J. Pharmacol. 498 (2004) 27-35
96. Mulligan J.D., Gonzalez A.A., Stewart A.M., Carey H.V., and Saupe K.W. Upregulation of AMPK during cold exposure occurs via distinct mechanism in brown and white adipose tissue. J. Physiol. 580 2 (2007) 677-684
97. Murakami N., Hayashida T., Kuroiwa T., Nakahara K., Ida T., Mondal M.S., Nakazato M., Kojima M., and Kangawa K. Role for central ghrelin in food intake and secretion profile of stomach ghrelin in rats. J. Endocrinol. 174 (2002) 283-288
98. Murata M., Okimura Y., Iida K., Matsumoto M., Sowa H., Kaji H., Kojima M., Kangawa K., and Chihara K. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J. Biol. Chem. 277 (2002) 5667-5674
99. Murata M., Okimura Y., Iida K., Matsumoto M., Sowa H., Kaji H., Kojima M., Kangawa K., and Chihara K. Ghrelin modulates the downstream molecules of insulin signaling in hepatoma cells. J. Biol. Chem. 277 (2002) 5667-5674
100. Nagaya N., Kojima M., Uematsu M., Yamagishi M., Hosoda H., Oya H., Hayashi Y., and Kangawa K. Hemodynamic and hormonal effects of human ghrelin in healthy volunteers. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280 (2001) R1483-R1487
101. Nakazato M., Murakami N., Date Y., Kojima M., Matsuo H., Kangawa K., and Matsukura S. A role for ghrelin in the central regulation of feeding. Nature 409 (2001) 194-198
102. Oka S., Tsuchie A., Tokumura A., Muramatsu M., Suhara Y., Takayama H., Waku K., and Sugiura T. Ether-linked analogue of 2-arachidonoylglycerol (noladin ether) was not detected in the brains of various mammalian species. J. Neurochem. 85 (2003) 1374-1381
103. Okada K., Ishii S., Minami S., Sugihara H., Shibasaki T., and Wakabayashi I. Intracerebroventricular administration of the growth hormone-releasing peptide KP-102 increases food intake in free-feeding rats. Endocrinology 137 (1996) 5155-5158
104. Okumura H., Nagaya N., Enomoto M., Nakagawa E., Oya H., and Kangawa K. Vasodilatory effect of ghrelin, an endogenous peptide from the stomach. J. Cardiovasc. Pharmacol. 39 (2002) 779-783
105. Osei-Hyiaman D., Depetrillo M., Pacher P., Liu J., Radaeva S., Batkai S., Harvey-White J., Mackie K., Offertaler L., Wang L., and Kunos G. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J. Clin. Invest. 115 (2005) 1298-1305
106. Otto B., Cuntz U., Fruehauf E., Wawarta R., Folwaczny C., Riepl R.L., Heiman M.L., Lehnert P., Fichter M., and Tschop M. Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa. Eur. J. Endocrinol. 145 (2001) 669-673
107. Overduin J., Frayo R.S., Grill H.J., Kaplan J.M., and Cummings D.E. Role of the duodenum and macronutrient type in ghrelin regulation. Endocrinology 146 (2005) 845-850
108. Pacher P., Batkai S., and Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 58 (2006) 389-462
109. Pemberton C.J., Tokola H., Bagi Z., Koller A., Pontinen J., Ola A., Vuolteenaho O., Szokodi I., and Ruskoaho H. Ghrelin induces vasoconstriction in the rat coronary vasculature without altering cardiac peptide secretion. Am. J. Physiol. Heart Circ. Physiol. 287 (2004) H1522-H1529
110. Penicaud L., Leloup C., Fioramonti X., Lorsignol A., and Benani A. Brain glucose sensing: A subtle mechanism. Curr. Opin. Clin. Nutr. Metab. Care 9 (2006) 458-462
111. Perreault M., Istrate N., Wang L., Nichols A.J., Tozzo E., and Stricker-Krongrad A. Resistance to the orexigenic effect of ghrelin in dietary-induced obesity in mice: Reversal upon weight loss. Int. J. Obes. Relat. Metab. Disord. 28 (2004) 879-885
112. Pettersson I., Muccioli G., Granata R., Deghenghi R., Ghigo E., Ohlsson C., and Isgaard J. Natural (ghrelin) and synthetic (hexarelin) GH secretagogues stimulate H9c2 cardiomyocyte cell proliferation. J. Endocrinol. 175 (2002) 201-209
113. Pi-Sunyer F.X., Aronne L.J., Heshmati H.M., Devin J., and Rosenstock J. 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 295 (2006) 761-775
114. Poykko S.M., Kellokoski E., Ukkola O., Kauma H., Paivansalo M., Kesaniemi Y.A., and Horkko S. Plasma ghrelin concentrations are positively associated with carotid artery atherosclerosis in males. J. Intern. Med. 260 (2006) 43-52
115. Purnell J.Q., Weigle D.S., Breen P.A., and Cummings D.E. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J. Clin. Endocrinol. Metab. 88 (2003) 5747-5752
116. Ravussin E., Tschop M., Morales S., Bouchard C., and Heiman M.L. Plasma ghrelin concentration and energy balance: Overfeeding and negative energy balance studies in twins. J. Clin. Endocrinol. Metab. 86 (2001) 4547-4551
117. Russell III R.R., Li J., Coven D.L., Pypaert M., Zechner C., Palmeri M., Giordano F.J., Mu J., Birnbaum M.J., and Young L.H. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. J. Clin. Invest. 114 (2004) 495-503
118. Sanchis-Segura C., Cline B.H., Marsicano G., Lutz B., and Spanagel R. Reduced sensitivity to reward in CB1 knockout mice. Psychopharmacology (Berl.) 176 (2004) 223-232
119. Scheen A.J., Finer N., Hollander P., Jensen M.D., and Van Gaal L.F. Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: A randomised controlled study. Lancet 368 (2006) 1660-1672
120. Schutte A.E., Huisman H.W., Schutte R., van Rooyen J.M., Malan L., and Malan N.T. Aging influences the level and functions of fasting plasma ghrelin levels: The POWIRS-Study. Regul. Pept. 139 (2007) 65-71
121. Shibasaki T., Yamauchi N., Takeuchi K., Ishii S., Sugihara H., and Wakabayashi I. The growth hormone secretagogue KP-102-induced stimulation of food intake is modified by fasting, restraint stress, and somatostatin in rats. Neurosci. Lett. 255 (1998) 9-12
122. Shiiya T., Nakazato M., Mizuta M., Date Y., Mondal M.S., Tanaka M., Nozoe S., Hosoda H., Kangawa K., and Matsukura S. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J. Clin. Endocrinol. Metab. 87 (2002) 240-244
123. Shuto Y., Shibasaki T., Otagiri A., Kuriyama H., Ohata H., Tamura H., Kamegai J., Sugihara H., Oikawa S., and Wakabayashi I. Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity. J. Clin. Invest. 109 (2002) 1429-1436
124. Simiand J., Keane M., Keane P.E., and Soubrie P. SR 141716, a CB1 cannabinoid receptor antagonist, selectively reduces sweet food intake in marmoset. Behav. Pharmacol. 9 (1998) 179-181
125. Sipe J.C., Waalen J., Gerber A., and Beutler E. Overweight and obesity associated with a missense polymorphism in fatty acid amide hydrolase (FAAH). Int. J. Obes. (Lond.) 29 (2005) 755-759
126. Steffens S., and Mach F. Cannabinoid receptors in atherosclerosis. Curr. Opin. Lipidol. 17 (2006) 519-526
127. Steffens S., Veillard N.R., Arnaud C., Pelli G., Burger F., Staub C., Karsak M., Zimmer A., Frossard J.L., and Mach F. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434 (2005) 782-786
128. Sturm K., MacIntosh C.G., Parker B.A., Wishart J., Horowitz M., and Chapman I.M. Appetite, food intake, and plasma concentrations of cholecystokinin, ghrelin, and other gastrointestinal hormones in undernourished older women and well-nourished young and older women. J. Clin. Endocrinol. Metab. 88 (2003) 3747-3755
129. Sugiura T., Kondo S., Sukagawa A., Nakane S., Shinoda A., Itoh K., Yamashita A., and Waku K. 2-Arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215 (1995) 89-97
130. Sun Y., Ahmed S., and Smith R.G. Deletion of ghrelin impairs neither growth nor appetite. Mol. Cell. Biol. 23 (2003) 7973-7981
131. Sun Y., Wang P., Zheng H., and Smith R.G. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc. Natl. Acad. Sci. USA 101 (2004) 4679-4684
132. Teff K.L., Elliott S.S., Tschop M., Kieffer T.J., Rader D., Heiman M., Townsend R.R., Keim N.L., D'Alessio D., and Havel P.J. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J. Clin. Endocrinol. Metab. 89 (2004) 2963-2972
133. Thompson N.M., Gill D.A., Davies R., Loveridge N., Houston P.A., Robinson I.C., and Wells T. Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor. Endocrinology 145 (2004) 234-242
134. Torsello A., Luoni M., Schweiger F., Grilli R., Guidi M., Bresciani E., Deghenghi R., Muller E.E., and Locatelli V. Novel hexarelin analogs stimulate feeding in the rat through a mechanism not involving growth hormone release. Eur. J. Pharmacol. 360 (1998) 123-129
135. Tschop M., Smiley D.L., and Heiman M.L. Ghrelin induces adiposity in rodents. Nature 407 (2000) 908-913
136. Tschop M., Wawarta R., Riepl R.L., Friedrich S., Bidlingmaier M., Landgraf R., and Folwaczny C. Post-prandial decrease of circulating human ghrelin levels. J. Endocrinol. Invest. 24 (2001) RC19-RC21
137. Tschop M., Weyer C., Tataranni P.A., Devanarayan V., Ravussin E., and Heiman M.L. Circulating ghrelin levels are decreased in human obesity. Diabetes 50 (2001) 707-709
138. Tucci S.A., Rogers E.K., Korbonits M., and Kirkham T.C. The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin. Br. J. Pharmacol. 143 (2004) 520-523
139. Tups A., Helwig M., Khorooshi R.M., Archer Z.A., Klingenspor M., and Mercer J.G. Circulating ghrelin levels and central ghrelin receptor expression are elevated in response to food deprivation in a seasonal mammal (Phodopus sungorus). J. Neuroendocrinol. 16 (2004) 922-928
140. Underdown N.J., Hiley C.R., and Ford W.R. Anandamide reduces infarct size in rat isolated hearts subjected to ischaemia-reperfusion by a novel cannabinoid mechan-ism. Br. J. Pharmacol. 146 (2005) 809-816
141. Van Gaal L.F., Rissanen A.M., Scheen A.J., Ziegler O., and Rossner S. 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 365 (2005) 1389-1397
142. Van Sickle M.D., Duncan M., Kingsley P.J., Mouihate A., Urbani P., Mackie K., Stella N., Makriyannis A., Piomelli D., Davison J.S., Marnett L.J., Di Marzo V., et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310 (2005) 329-332
143. Vavvas D., Apazidis A., Saha A.K., Gamble J., Patel A., Kemp B.E., Witters L.A., and Ruderman N.B. Contraction-induced changes in acetyl-CoA carboxylase and 5′-AMP-activated kinase in skeletal muscle. J. Biol. Chem. 272 (1997) 13255-13261
144. Walsh D., Nelson K.A., and Mahmoud F.A. Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer 11 (2003) 137-143
145. Weekers F., Van Herck E., Isgaard J., and Van den B.G. Pretreatment with growth hormone-releasing peptide-2 directly protects against the diastolic dysfunction of myocardial stunning in an isolated, blood-perfused rabbit heart model. Endocrinology 141 (2000) 3993-3999
146. Weigle D.S., Cummings D.E., Newby P.D., Breen P.A., Frayo R.S., Matthys C.C., Callahan H.S., and Purnell J.Q. Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J. Clin. Endocrinol. Metab. 88 (2003) 1577-1586
147. Wiley K.E., and Davenport A.P. Comparison of vasodilators in human internal mammary artery: Ghrelin is a potent physiological antagonist of endothelin-1. Br. J. Pharmacol. 136 (2002) 1146-1152
148. Williams C.M., and Kirkham T.C. Observational analysis of feeding induced by Delta9-THC and anandamide. Physiol. Behav. 76 (2002) 241-250
149. Williams D.L., Grill H.J., Cummings D.E., and Kaplan J.M. Overfeeding-induced weight gain suppresses plasma ghrelin levels in rats. J. Endocrinol. Invest. 29 (2006) 863-868
150. Winder W.W., and Hardie D.G. Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise. Am. J. Physiol. 270 (1996) E299-E304
151. Witczak C.A., Fujii N., Hirshman M.F., and Goodyear L.J. CaMKK{alpha} regulates skeletal muscle glucose uptake independent of AMPK and Akt activation. Diabetes 56 5 (2007) 1403-1409
152. Woods A., Dickerson K., Heath R., Hong S.P., Momcilovic M., Johnstone S.R., Carlson M., and Carling D. C(Ca2+)/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2 (2005) 21-33
153. Wortley K.E., Anderson K.D., Garcia K., Murray J.D., Malinova L., Liu R., Moncrieffe M., Thabet K., Cox H.J., Yancopoulos G.D., Wiegand S.J., and Sleeman M.W. Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc. Natl. Acad. Sci. USA 101 (2004) 8227-8232
154. Wortley K.E., del Rincon J.P., Murray J.D., Garcia K., Iida K., Thorner M.O., and Sleeman M.W. Absence of ghrelin protects against early-onset obesity. J. Clin. Invest. 115 (2005) 3573-3578
155. Wren A.M., Small C.J., Ward H.L., Murphy K.G., Dakin C.L., Taheri S., Kennedy A.R., Roberts G.H., Morgan D.G., Ghatei M.A., and Bloom S.R. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 141 (2000) 4325-4328
156. Wren A.M., Small C.J., Thomas E.L., Abbott C.R., Ghatei M.A., Bell J.D., and Bloom S.R. Continuous subcutaneous administration of ghrelin results in accumulation of adipose tissue, independent of hyperphagiaor bodyweight gain. Endocrine Abstracts Spring (2004) OC35 (Abstract)
157. Yin W., Mu J., and Birnbaum M.J. Role of AMP-activated protein kinase in cyclic AMP-dependent lipolysis In 3T3-L1 adipocytes. J. Biol. Chem. 278 (2003) 43074-43080
158. Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108 (2001) 1167-1174
159. Zong H., Ren J.M., Young L.H., Pypaert M., Mu J., Birnbaum M.J., and Shulman G.I. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc. Natl. Acad. Sci. USA 99 (2002) 15983-15987