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Role of the corticotropin-releasing factor receptor type 2 in the control of food intake in mice: a meal pattern analysis


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    Present address: Service Endocrinologie, USN Haut Leveque, Avenue Magellan, 33604 Pessac, France

Dr Antoine Tabarin, at present address below.


The actions of corticotropin-releasing factor (CRF) and related peptides are mediated by two receptors (CRF1 and CRF2). The respective role of each subtype in the control of food intake remains poorly known. In the present study, we examined the quantity and microstructure of ingestive behavior of knockout (KO) mice lacking CRF2 receptors and their wild-type (WT) littermates. Under basal conditions, CRF2 KO mice showed increased nocturnal food intake, evident as an increased zenith in circadian cosinor analysis of food intake. Microstructure analysis revealed that this greater food intake reflected increased meal size, rather than meal frequency, suggesting a decreased satiating value of food. Following acute restraint stress, CRF2 KO mice showed an intact immediate anorectic response with increased latency to eat and decreased meal size. However, CRF2 deletion abolished the prolonged phase of restraint-induced anorexia. CRF2 KO mice did not differ from WT controls in feeding responses to food deprivation or injection of ghrelin receptor agonists. Independent of genotype, food deprivation increased food intake, with dramatic changes in meal size, meal frequency, water : food ratio and eating rate. Acyl-ghrelin or BIM-28131, a potent ghrelin analog, dose-dependently stimulated food intake by increasing meal size (ghrelin, BIM-28131) and meal number (BIM-28131), while slowing the average eating rate (BIM-28131) similarly in WT and KO mice. These results suggest that the CRF2 receptor is involved in the control of meal size during the active phase of eating and following acute exposure to stress.