Ghrelin and cannabinoids require the ghrelin receptor to affect cellular energy metabolism
Copyright policy )Ghrelin and cannabinoids require the ghrelin receptor to affect cellular energy metabolism
Ghrelin is a potent orexigenic brain-gut peptide with lipogenic and diabetogenic effects, possibly mediated by growth hormone secretagogue receptor (GHS-R1a). Cannabinoids also have orexigenic and lipogenic effects. AMPK is a regulator of energy homeostasis and we have previously shown that ghrelin and cannabinoids stimulate hypothalamic AMPK activity while inhibiting it in the liver and adipose tissue, suggesting that AMPK mediates both the central appetite-inducing and peripheral effects of ghrelin and cannabinoids.Using GHS-R KO mice, we investigated whether the known ghrelin receptor GHS-R1a is required for the tissue-specific effects of ghrelin on AMPK activity, and if an intact ghrelin signalling pathway is necessary for the effects of cannabinoids on AMPK activity.Wild-type and GHS-R KO mice were treated intraperitoneally with ghrelin 500 ng/g bodyweight or CB1 agonist HU210 20 ng/g and hypothalamic, hepatic and adipose AMPK activity was studied using a functional kinase assay.Ghrelin and HU210 significantly stimulated hypothalamic AMPK activity in wild-type animals (mean±SEM, 122.5±5.2% and 128±11.6% of control, p0.05).Ghrelin requires GHS-R1a for its effect on hypothalamic, liver and adipose tissue AMPK activity. An intact ghrelin signalling pathway is necessary for the effects of cannabinoids on AMPK activity.
- William Harvey Research Institute United Kingdom
- University of Cincinnati United States
- Oxford Centre for Diabetes, Endocrinology and Metabolism United Kingdom
- Queen Mary University of London United Kingdom
- Institute for Diabetes and Obesity Germany
Male, Hypothalamus, Subcutaneous Fat, Gene Expression, Intra-Abdominal Fat, Biochemistry, Article, Mice, Endocrinology, Receptor, Cannabinoid, CB1, Animals, Dronabinol, Receptors, Ghrelin, Molecular Biology, Cannabinoid Receptor Agonists, Mice, Knockout, Adenylate Kinase, Ghrelin, Mice, Inbred C57BL, Liver, Energy Intake, Energy Metabolism, Signal Transduction
Male, Hypothalamus, Subcutaneous Fat, Gene Expression, Intra-Abdominal Fat, Biochemistry, Article, Mice, Endocrinology, Receptor, Cannabinoid, CB1, Animals, Dronabinol, Receptors, Ghrelin, Molecular Biology, Cannabinoid Receptor Agonists, Mice, Knockout, Adenylate Kinase, Ghrelin, Mice, Inbred C57BL, Liver, Energy Intake, Energy Metabolism, Signal Transduction
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