TY - JOUR
T1 - The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release
AU - Kola, Blerina
AU - Wittman, Gábor
AU - Bodnár, Ibolya
AU - Amin, Faisal
AU - Lim, Chung Thong
AU - Oláh, Márk
AU - Christ-Crain, Mirjam
AU - Lolli, Francesca
AU - Van Thuijl, Hinke
AU - Leontiou, Chrysanthia A.
AU - Füzesi, Tamás
AU - Dalino, Paolo
AU - Isidori, Andrea M.
AU - Harvey-White, Judith
AU - Kunos, George
AU - Nagy, György M.
AU - Grossman, Ashley B.
AU - Fekete, Csaba
AU - Korbonits, Márta
PY - 2013/12
Y1 - 2013/12
N2 - 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.-Kola, B., Wittman, G., Bodnár, I., Amin, F., Lim, C. T., Oláh, M., Christ-Crain, M., Lolli, F., van Thuijl, H., Leontiou, C. A., Füzesi, T., Dalino, P., Isidori, A. M., Harvey-White, J., Kunos, G., Nagy, G. M., Grossman, A. B., Fekete, C., Korbonits, M. The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release.
AB - 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.-Kola, B., Wittman, G., Bodnár, I., Amin, F., Lim, C. T., Oláh, M., Christ-Crain, M., Lolli, F., van Thuijl, H., Leontiou, C. A., Füzesi, T., Dalino, P., Isidori, A. M., Harvey-White, J., Kunos, G., Nagy, G. M., Grossman, A. B., Fekete, C., Korbonits, M. The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release.
KW - Cannabinoids
KW - CB1 knockout
KW - Rimonabant
UR - http://www.scopus.com/inward/record.url?scp=84890490107&partnerID=8YFLogxK
U2 - 10.1096/fj.13-232918
DO - 10.1096/fj.13-232918
M3 - Article
C2 - 23982145
AN - SCOPUS:84890490107
SN - 0892-6638
VL - 27
SP - 5112
EP - 5121
JO - FASEB Journal
JF - FASEB Journal
IS - 12
ER -