Lack of CCK1R reduces satiation in response to dietary fat

Abstract

Food intake is regulated by signals coming from the gastrointestinal tract and by the brain. There is good evidence that long term consumption of a high fat diet leads to desensitization in detection of dietary lipid, possibly by a decrease in vagal afferent sensitivity to cholecystokinin (CCK). We tested the hypothesize that CCK acting at CCK1 receptors is essential for response to a high fat diet using CCK1R−/ − mice. CCK1R−/ − mice or their wildtypes 129sv were maintained on isocaloric high fat (HF) or isocaloric normal fat (NF) diets for 4 weeks and meal pattern analysis was performed using the Habitest system. There was no significant difference in overall daily food intake or weight gain between the two groups. The CCK1R−/ − mice fed either the NF or the HF diet consumed significantly more food in the first meal compared to the wildtype controls (64% and 60% of total food intake vs. 51% and 46%). During the second meal, the CCK1R−/ − mice fed the HF diet consumed twice as much food as the controls; there was no difference between CCK1R−/ − or wildtype mice fed the NF diet. These results indicate that CCK1R−/ − mice fed a high fat diet are less satiated compared to wildtype mice. We conclude that the CCK1R is involved in satiation in response to a high fat diet.