Loss of cholecystokinin and glucagon-like peptide-1-induced satiation in mice lacking serotonin 2C receptors.
To investigate the role of serotonin 2C receptors (2CR), which are expressed only in the central nervous system, in the satiating actions of the gut peptides CCK and glucagon-like peptide 1 (GLP-1), we examined 1) the effect of null mutations of serotonin 2CR (2CR KO) on the eating-inhibitory potencies of dark-onset intraperitoneal injections of 0.9, 1.7, or 3.5 nmol/kg (1, 2, or 4 microg/kg) CCK and 100, 200, and 400 nmol/kg (33, 66, or 132 microg/kg) GLP-1, and 2) the effects of intraperitoneal injections of 1.7 nmol//kg CCK and 100 nmol/kg GLP-1 on neuronal activation in the brain, as measured by c-Fos expression. All CCK and GLP-1 doses decreased 30-min food intake in wild-type (WT) mice, but none of them did in 2CR KO mice. CCK increased the number of cells expressing c-Fos in the nucleus tractus solitarii (NTS) of WT, but not 2CR KO mice. CCK induced similar degrees of c-Fos expression in the paraventricular (PVN) and arcuate (Arc) nuclei of the hypothalamus of both genotypes. GLP-1, on the other hand, increased c-Fos expression similarly in the NTS of both genotypes and increased c-Fos expression more in the PVN and Arc of 2CR KO mice, but not WT mice. These results indicate that serotonin signaling via serotonin 2CR is necessary for the full satiating effects of CCK and GLP-1. In addition, they suggest that the satiating effects of the two peptides are mediated by different neural mechanisms.
Asarian
Lori
L
Physiology and Behavior Group, ETH-Zürich, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland. lasarian@ethz.ch
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000378:metabolism*; D004435:Eating; D005247:Feeding Behavior; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000172:deficiency* / Q000235:genetics; D012527:Satiation; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D017552:Solitary Nucleus / Q000378:metabolism; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D044405:Receptor, Serotonin, 5-HT2C; D012701:Serotonin; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin