SFEBES2008 Oral Communications Young Endocrinologist prize session (8 abstracts)
The ghrelin-cannabinoid axis: a novel pathway in the regulation of appetite and metabolism
Faisal Amin 1 , Blerina Kola 1 , Mirjam Christ-Crain 1 , Francesca Lolli 1 , Gabor Wittmann 2 , Judith Harvey-White 3 , George Kunos 3 , Ashley B Grossman 1 , Csaba Fekete 4 & Marta Korbonits 1
1Centre for Endocrinology, William Harvey Research Institute, Barts and the London Medical School, London, UK; 2Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary; 3Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, USA; 4Tupper Research Institute and Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tufts-New England Medical Center, Boston, USA.
We have previously shown that the orexigenic and peripheral adipogenic effects of ghrelin are mediated by its effect on the metabolic enzyme AMPK. As the cannabinoid (CB1)-antagonist rimonabant inhibits the orexigenic effect of ghrelin, we suggest that there is an interaction between cannabinoids and ghrelin.
To study the involvement of CB1 in the effects of ghrelin, wild-type (WT) and CB1-knockout mice were treated with ghrelin and rimonabant.
Ghrelin injection did not increase the food intake of CB1-KO animals (ghrelin 0.42±0.07 g, control 0.41±0.1 g), while WT animals showed the expected augmented food intake (ghrelin 1.0±0.08 g, control 0.62±0.1 g, P<0.05). Ghrelin significantly increased the 2-AG content of the hypothalamus in WT mice (30.3±2.4 pmol/mg tissue, control 21.7±1.8 pmol/mg) and this effect was abolished by rimonabant pre-treatment (15.0±1.94 pmol/mg, P<0.001). No effect was observed in CB1-KO animals.
In WT animals ghrelin increased AMPK activity in the hypothalamus (143.2±11% of control, P<0.01), confirming previous data, and this effect was blocked by rimonabant pre-administration (94.7±6.9%). In the CB1-KO animals, hypothalamic AMPK activity was not affected by ghrelin. In WT mice ghrelin administration inhibited AMPK activity in fat tissue (58.5±5.7%), while co-administration of rimonabant antagonised this effect. In CB1-KO animals ghrelin did not change AMPK activity in fat tissue.
In conclusion, using both pharmacological and genetic approaches we demonstrate that an intact cannabinoid signaling pathway is necessary for the stimulatory effects of ghrelin on hypothalamic AMPK activity, for the stimulatory effect on hypothalamic cannabinoid content and therefore for the increased effect on food intake. We have also shown that there is a tight interaction between the cannabinoid and ghrelin systems in the periphery, as CB1 is necessary for the effect of ghrelin on adipose tissue AMPK activity. These data support the existence of a novel ‘ghrelin→CB1→AMPK→metabolism’ pathway.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more