Effects of oral preload, CCK or bombesin administration on short term food intake of melanocortin 4-receptor knockout (MC4RKO) mice.
We investigated whether either heterozygous (HET) or homozygous (knockout, KO) disruption of the melanocortin type 4 receptor (MC4R) gene alters post ingestive responsiveness of mice. Specifically, we tested the hypothesis that hyperphagia in MC4RKO mice might be due to a deficit in processes that sustain intermeal intervals (satiety) and/or processes that terminate ongoing episodes of eating (satiation). To test satiety, mice drank an oral preload and then we monitored intake of a subsequent liquid diet test meal. To test satiation, we examined the effect of exogenous administration of cholecystokinin (CCK) and bombesin (BN) on the size of a liquid diet meal. Experiment 1 was comprised of two studies. In the first, we determined that the intake of all three genotypes following fasts of either 6, 12, or 24h were comparable, and so chose 12h deprivation for the subsequent studies. In the second, 12h fasted mice were allowed to consume a fixed preload, approximately 50% of their expected mean intake and, following delays of either 30 or 60 min, were allowed to consume to satiation. Compared with no preload, the preload significantly reduced meal size comparably in all three genotypes. The reduction in intake was greater when the test meal was presented 30 compared with 60 min after the preload, again with no genotype differences in this decay of satiety. In experiment 2, we administered either CCK or BN and examined suppression of meal size after a 12h fast. Mice were tested repeatedly with CCK-8 (2, 6, or 18 microg/kg ip) or BN (2, 4 or 8 microg/kg ip) with vehicle injection days intervening. The 30 min intakes of HET and KO mice were suppressed more than those of WT following either CCK or BN. These experiments suggest that diminished responsiveness to nutrients or gut satiety hormones is not responsible for hyperphagia in MC4RKO mice.
Vaughan
C H
CH
Department of Psychology, University of Florida, Gainesville, FL 32611, USA.
Haskell-Luevano
C
C
Andreasen
A
A
Rowland
N E
NE
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000502:physiology*; D002766:Cholecystokinin / Q000008:administration & dosage / Q000502:physiology*; D004435:Eating / Q000235:genetics*; D006963:Hyperphagia / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency / Q000235:genetics*; D012528:Satiety Response / Q000502:physiology
D044105:Receptor, Melanocortin, Type 4; D002766:Cholecystokinin; D001839:Bombesin