ENDOKANABİNOİD SİSTEMİN , ENERJİ METABOLİZMASI VE OBEZİTEYE ETKİSİ

Yıl 2007, Cilt: 20 Sayı: 3, 202 - 214, 25.06.2015

Emel Tüfekçi Alphan , Nevin Yılmaz

Öz

Son zamanlarda hint keneviri ve onun majör psikotropik komponenti olan, ∆9-tetrahidrokanabinol, KB1 kanabinoid reseptörleri ve endojen bağlarını içeren endokanabinoidlerin, enerji dengesini kontrol ederek iştahı stimüle ettiği ve vücut ağırlığını artırdığı belirlenmiştir. Hayvan çalışmalarında ve insanlarda yapılan klinik çalışmalarda, endokanabinoid sistemin, besin alımını santral ve periferik mekanizmalarla kontrol ettiği, lipogenez ve yağ birikimini stimüle ettiği gösterilmiştir. Bu makalede, endokanabinoid sistemin oluşumu, reseptörleri, bağları ve bu fizyolojik sistemin enerji metabolizması ve obezite üzerine olan etkisi tartışılmıştır.

Anahtar Kelimeler: Endokanabinoid system, Esrar, Obezite , Enerji metabolizması

Anahtar Kelimeler

Endokanabinoid system, Esrar, Obezite , Enerji metabolizması

Kaynakça

• Pagotta U, Vicennati V, Pasquali R. The
• endocannabinoid system and the treatment of obesity.
• Annals of Medicine; 2005:270-275.
• Define Understand Ackowledge Highligt Review. The
• Endocannabinoid System and the Regulation of Energy
• Metabolism. Eds: Jorge Plutzky and Stephen C. Woods.
• Brought by Sanofi-Aventis U.S.LLC. Diabetes Care
• ;(9)
• Cota D, Woods SC. The role of the endocannabinoid
• system in the regulation of energy homeostasis.
• Endocrinology and Diabetes 2005;12 (5):338-351.
• Ravinet-Tirollou C, Delgorge C, Menet C, Arnone M,
• Soubrie P. CB1 cannabinoid receptor knockout in mice
• leads to leannes, resistance to diet-induced obesity and
• enhanced leptin sensitivity. Internal Journal Obesity
• Related Metabolic Disorder 2004;28:640-648.
• Ravinet-Trillou C, Arnone M, Delgorge C, Gonalans N,
• Keane P, Maffrand JP, Soubrie P. Anti-obesity effect of
• SR141716, a CB1 receptor antagonist, in diet-induced
• obese mice. American Journal Physiology Regul Integr
• Comp Physiology 2003;284:R345-R353.
• Di Marzo V, Bifulco M, De Petrocellis L. The
• endocannabinoid system and its therapeutic exploitation.
• Naturel Reviews/ Drug Discovery 2004;3:771-84.
• 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;112:423-31
• Sarnataro D, Pisanti S, Santoro A, Gazzerro P,
• Malfitano AM, Laezza C, Bifulco M. The Cannabinoid
• CB1 Receptor Antagonist Rimonabant (SR141716)
• Inhibits Human Breast Cancer Cell Proliferation through
• a Lipid Raft-Mediated Mechanism Mol Pharmacol
• ; 70:1298-1306,
• -
• Marmara Medical Journal 2007;20(3);202-214
• Emel Tüfekçi Alphan, ark.
• Endokanabinoid sistemin , enerji metabolizması ve obeziteye etkisi
• Mechoulam R, Berry EM, Avraham Y, Marzo VD,
• Fride E. The Endocannabinoid System, mechanism of
• action and Function. Endocannabinoids, feeding and
• suckling-from our perspective. International Journal of
• Obesity 2006;30:24-28.
• Mattes RD, Engelman K, Shaw LM, Elsohly MA.
• Cannabinoids and appetite stimulation. Pharmacol
• Biochem Behav 49:187–195, 1994.
• Osei-Hyiaman D, l DePetrilloM, Pacher P, Liu J,
• Radaeva S, Bátkai S, Harvey-White J,Mackie K,
• Offertáler L, Wang L, Kunos G. Endocannabinoid
• activation at hepatic CB1 receptors stimulates fatty acid
• synthesis and contributes to diet-induced obesity.
• Journal of Clinical Investigation 2005 ;115:1298–1305.
• Howlett A C, Barth F, Bonner TI, Cabral G, Casellas P,
• Devane WA, Felder CC, Herkenham M, Mackie K,
• Martin BR, Mechoulam R, Pertwee RG. International
• Union of Pharmacology. XXVII. Classification of
• Cannabinoid Receptors. International Union
• Pharmacology 2002; 54 (2):161-202.
• Gıuffrıda A, Beltramo M, Pıomellı D. Mechanisms of
• Endocannabinoid Inactivation: Biochemistry and
• Pharmacology. The Journal of Pharmacology and
• Experımental Therapeutıcs 2001;298:7–14.
• Korner J, Aronne LJ. The emerging science of body
• weight regulation and its impact on obesity treatment.
• Journal Cilinical Investigation 2003;111:565-570.
• Faroogi IS, O’Rahilly S. Recent advances in the genetics
• of severe childhood obesity. Arch Dis Child 2000; 83:
• -34.
• Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S,
• Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T,
• Kunos G. Leptin-regulated endocannabinoids are
• involved in maintaining food intake. Nature (London).
• ;410:822–825.
• Fride E, BregmanT, Tim Kirkham TC.
• Endocannabinoids and Food Intake: Newborn Suckling
• and Appetite Regulation in Adulthood. Experimental
• Biology and Medicine 2005;230:225-234.
• Kola B, Hubina E, Tucci SA, Kirkham TC, Garcia EA,
• Mitchell SE, Williams LM, Hawley SA, Hardie DG,
• Grossman AB, Korbonits M. Cannabinoids and Ghrelin
• Have Both Central and Peripheral Metabolic and
• Cardiac Effects via AMP-activated Protein Kinase.
• J.Biol.Chem.,2005;280(26):25196-25201.
• Jamshidi N, Taylor DA. Anandamid administration into
• the ventromedial hypotalamıus stimulates appetite in
• rats. British Journal Pharmacology 2001;134:1151-1154.
• Kirkham TC, Williams CM, Feza F, Marzo V.
• Endocannabinoid levels in rat limbic forebrain and
• hypothalamus in relation to fasting, feeding and satiation
• : stimulation of eating by arachidonoyl glycerol. British
• Journal Pharmacology 2002;136:550-557.
• Sato M, Suziki S, Senoo H. Hepatic stellate cells: unique
• characteristics in cell biology and phenotype. Cell Struct
• Funct. 2003;28:105-112.
• Hao S, Avraham Y, Mechoulam R, Berry EM. Low dose
• anandamide affects food intake, cognitive function,
• neurotransmitter and corticosterone levels in dietrestricted
• mice. Eur J Pharmacology 2000;392:147-156.
• Powell EE, Jonsson JR, Clouston AD. Steatosis: Cofactor
• in other liver disease .An update. Annals of
• Hepatology 2005;42: 5-13.
• Valdes DZ, Rodriquez GP, Tapia NCC, et al.The
• endocannabinoid system in chronic liver disease .
• Annals of Hepatology 2005;42:248-254.
• Sipe JC, Waalen J, Gerber A, et al.Oweweight and
• obesity associated with a missense polymorphism in
• fatty acid amide hydrolase (FAAH). Internal Journal
• Obesity Related Metabolic Disorders 2005;29:755-759.
• Engeli S, Bohnke J, Feldpausch M, et al. Activation of
• the peripheral endocannabinoid system in human
• obesity. Diabetes 2005;54:2838-2843.
• Bensaid M, Gary-Bobo M, Esclangon A, et al. The
• cannabinoid CB1 receptor antagonist SR141716
• increases Acrp30 mRNA expression in adipose tissue of
• obese fa/fa rats and cultured adipocyte cells. Mol
• Pharmacology 2003;63:908-914.
• Lichtman AH, Cravatt BF. Food for thought:
• endocannabinoid modulation of lipogenesis Journal
• Clinical Investigation 2005 ;115(5): 1130–1133.
• Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R.
• The emerging role of the endocannabinoid system in
• endocrine regulation and energy balance. Endocrine
• Reviews 2005; 27 (1): 73-100.
• Druce M, Bloom SR. The regulation of appetite.
• Archives of Disease in Childhood 2006;91:183-187.
• Williams CM, Kirkham TC. Anandamide induces
• overeating: mediation by central cannabinoid receptors.
• Psychopharmacology 1999;143:315-317.
• Pacher P, Bátkai S, Kunos G. The Endocannabinoid
• System as an Emerging Target of Pharmacotherapy.
• Pharmacol Rev 2006;58:389-462.
• 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 2005:1389-97.
• Despres JP, Golay A, Sjostorm L, et al. Effects of
• rimonabant on metabolic risk factors in overweight
• patients with dyslipidemia. New England Journal of
• Medicine 2005; 353:2121-2134.
• Pi-Sunyer FX, Aronne LJ, Heshmati HM et al. 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;295:761-775.
• Scheen AJ, Finer N, Hollander P, Jensen MD, Van Gaal
• LF, Efficacy and tolerability of rimonabant in
• overweight or obese patients with type 2 diabetes: a
• randomised controlled study The Lancet
• ;368:16601672.
• Cleland SJ, Sattar N. Does rimonabant pull its weight
• for type 2 diabetes? The Lancet 2006:368: 1632-1634.
• Horvath TL. Endocannabinoids and the regulation of
• body fat: the smoke is clearing. The Journal of Clinical
• Investigation. 2003 ;112:323–326.