Abstract
Ghrelin is an endogenous regulator of energy homeostasis synthesized by the stomach to stimulate appetite and positive energy balance. Similarly, the endocannabinoid system is part of our internal machinery controlling food intake and energy expenditure. Both peripheral and central mechanisms regulate CB1-mediated control of food intake and a functional relationship between hypothalamic ghrelin and cannabinoid CB1 receptor has been proposed. First of all, we investigated brain ghrelin actions on food intake in rats with different metabolic status (negative or equilibrate energy balance). Secondly, we tested a sub-anxiogenic ultra-low dose of the CB1 antagonist SR141716A (Rimonabant) and the peripheral-acting CB1 antagonist LH-21 on ghrelin orexigenic actions. We found that: 1) central administration of ghrelin promotes food intake in free feeding animals but not in 24 h food-deprived or chronically food-restricted animals; 2) an ultra-low dose of SR141716A (a subthreshold dose 75 folds lower than the EC50 for induction of anxiety) completely counteracts the orexigenic actions of central ghrelin in free feeding animals; 3) the peripheral-restricted CB1 antagonist LH-21 blocks ghrelin-induced hyperphagia in free feeding animals. Our study highlights the importance of the animaĺs metabolic status for the effectiveness of ghrelin in promoting feeding, and suggests that the peripheral endocannabinoid system may interact with ghrelińs signal in the control of food intake under equilibrate energy balance conditions.
Highlights
Ghrelin is a potent anabolic molecule with orexigenic and adipogenic actions
The test of within-subject contrast revealed no effect of time and ghrelin doses (F(3,96) = 0.28, P = 0.84) but an overall interaction between time and metabolic status (F(2,96) = 10,79, P = 0.0001), being the time after food presentation more influencing in those conditions where the animals were restricted for food
The main findings of this study are: a) ghrelin-induced orexigenic effects depends on the metabolic status of the animal, being effective in free feeding conditions but having no effect in animals under negative energy balance conditions such as fasted or chronically food-restricted rats; b) blockade of CB1 receptors at extremely low doses or with peripheralrestricted CB1 antagonists is able to counteract the hyperphagic effect of central ghrelin administration in free feeding animals
Summary
Ghrelin is a potent anabolic molecule with orexigenic and adipogenic actions. This hormone is produced in the periphery, mainly by the stomach and by lower parts of the gastrointestinal tract [1,2,3]. Within the central nervous system, ghrelin activates specific hypothalamic areas connecting with the orexigens neuropeptide Y, orexin, and Agouti-related peptide [4,5] and regulates growth hormone (GH) secretion and energy homeostasis [6]. The orexigenic actions of ghrelin administration are mainly known in the context of an equilibrated energetic balance but little is known about the role of this hormone in different feeding status where the energy intake is not equal to the energy expenditure
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
