title: The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release.
abstract: This study aimed to investigate whether the growth hormone release and metabolic effects of ghrelin on AMPK activity of peripheral tissues are mediated by cannabinoid receptor type 1 (CB1) and the central nervous system. CB1-knockout (KO) and/or wild-type mice were injected peripherally or intracerebroventricularly with ghrelin and CB1 antagonist rimonabant to study tissue AMPK activity and gene expression (transcription factors SREBP1c, transmembrane protein FAS, enzyme PEPCK, and protein HSL). Growth hormone levels were studied both in vivo and in vitro. Peripherally administered ghrelin in liver, heart, and adipose tissue AMPK activity cannot be observed in CB1-KO or CB1 antagonist-treated mice. Intracerebroventricular ghrelin treatment can influence peripheral AMPK activity. This effect is abolished in CB1-KO mice and by intracerebroventricular rimonabant treatment, suggesting that central CB1 receptors also participate in the signaling pathway that mediates the effects of ghrelin on peripheral tissues. Interestingly, in vivo or in vitro growth hormone release is intact in response to ghrelin in CB1-KO animals. Our data suggest that the metabolic effects of ghrelin on AMPK in peripheral tissues are abolished by the lack of functional CB1 receptor via direct peripheral effect and partially through the central nervous system, thus supporting the existence of a possible ghrelin-cannabinoid-CB1-AMPK pathway.
authors: 1Márta Korbonits, Dept. of Endocrinology, Barts and the London School of Medicine and Dentistry, Charterhouse Sq., London EC1M 6BQ, UK. m.korbonits@qmul.ac.uk.
authors: Blerina
authors: B
authors: Kola
authors: Gábor
authors: G
authors: Wittman
authors: Ibolya
authors: I
authors: Bodnár
authors: Faisal
authors: F
authors: Amin
authors: Chung Thong
authors: CT
authors: Lim
authors: Márk
authors: M
authors: Oláh
authors: Mirjam
authors: M
authors: Christ-Crain
authors: Francesca
authors: F
authors: Lolli
authors: Hinke
authors: H
authors: van Thuijl
authors: Chrysanthia A
authors: CA
authors: Leontiou
authors: Tamás
authors: T
authors: Füzesi
authors: Paolo
authors: P
authors: Dalino
authors: Andrea M
authors: AM
authors: Isidori
authors: Judith
authors: J
authors: Harvey-White
authors: George
authors: G
authors: Kunos
authors: György M
authors: GM
authors: Nagy
authors: Ashley B
authors: AB
authors: Grossman
authors: Csaba
authors: C
authors: Fekete
authors: Márta
authors: M
authors: Korbonits
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D013006:Growth Hormone / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000077285:Rimonabant; D014158:Transcription, Genetic
chemical_list: D063387:Cannabinoid Receptor Antagonists; D054439:Ghrelin; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013006:Growth Hormone; D055372:AMP-Activated Protein Kinases; D000077285:Rimonabant
keywords: CB1 knockout; cannabinoids; rimonabant
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