Complex Interplay between the Cannabinoid CB1 Receptor and Corticotropin-Releasing Hormone in the Regulation of Appetite, Food Intake and Energy Expenditure

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 649-675-Central Regulation of Appetite & Feeding/GI Regulatory Peptides
Bench to Bedside
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-671
Alexia V Polissidis*, Sevasti Karaliota and Katia/Catherine P Karalis
Biomedical Research Foundation of the Academy of Athens, Athens, Greece
Feeding behavior is a key component of energy balance and metabolism and is vital to our survival. Corticotropin Releasing Hormone or Factor (CRH/CRF) instigates the stress response by activating the hypothalamic-pituitary-adrenal axis (HPA axis), a process involved in the neural control of appetite and food intake. The endocannabinoid system (ECS) is a neuromodulatory system implicated in the maintenance of brain homeostasis and more specifically, a growing body of evidence strongly supports a regulatory role of the CB1 cannabinoid receptor in feeding behavior. Therefore, insight gained into the interaction between the CB1 receptor and CRH could aid our understanding of feeding processes and their dysregulation that leads to serious health issues such as eating disorders and obesity. Emerging evidence supports such an interaction between CRH and the CB1 receptor in food intake and energy homeostasis, however, our understanding of cannabinoid-induced orexigenic and pro-feeding effects in animal models and the role of the ECS in neural modulation of feeding and energy balance merits further investigation. The present study aims to elucidate the role of the CB1 receptor in regulation of appetite, food intake and metabolism with emphasis on its complex interplay with the HPA axis, specifically CRH. To this end, indirect calorimetry was performed using metabolic cages to monitor 24 hour metabolic activity during normal feeding, fasting and re-feeding conditions in adult male CRH deficient and wildtype mice following daily administration of the potent CB1 receptor agonist, HU210. Our most remarkable findings revealed a cannabinoid-induced biphasic effect on food intake. Particularly, we observed an acute (within 30 min) CRH-dependent cannabinoid-induced orexigenic/ hyperphagic effect following fasting, whereas in the long-term (24 h), HU210 administration was able to compensate for decreased food intake observed in CRH deficient mice during re-feeding. In addition, HU210 was able to counteract decreased fat and increased carbohydrate oxidation observed in CRH deficient mice during re-feeding, resulting in an overall reversal of their reduced respiratory exchange ratio. This data supports a complex modulatory interrelationship between the CB1 receptor and CRH in the regulation of food intake and metabolism characterized by differentiated effects between fast-acting feeding processes and long-lasting homeostatic metabolic mechanisms.

Nothing to Disclose: AVP, SK, KPK

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