The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release

Blerina Kola, Gábor Wittman, Ibolya Bodnár, Faisal Amin, Chung Thong Lim, Márk Oláh, Mirjam Christ-Crain, Francesca Lolli, Hinke Van Thuijl, Chrysanthia A. Leontiou, Tamás Füzesi, Paolo Dalino, Andrea M. Isidori, Judith Harvey-White, George Kunos, György M. Nagy, Ashley B. Grossman, Csaba Fekete, Márta Korbonits

Research output: Article

19 Citations (Scopus)

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.-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.

Original languageEnglish
Pages (from-to)5112-5121
Number of pages10
JournalFASEB Journal
Volume27
Issue number12
DOIs
Publication statusPublished - dec. 1 2013

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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. (2013). The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release. FASEB Journal, 27(12), 5112-5121. https://doi.org/10.1096/fj.13-232918