CCK1 receptor is essential for normal meal patterning in mice fed high fat diet

Abstract Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK1 Rs) located on vagal afferent nerve terminals located in the wall of the gastrointestinal tract. In the present study, we determined the role of the CCK1 R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK1 R gene is deleted. CCK1 R−/− and CCK1 R+/+ mice were fed isocaloric high fat (HF) or low fat (LF) diets ad libitum for 18 h each day and meal size, meal frequency, intermeal interval, and meal duration were determined. Daily food intake was unaltered by diet in the CCK1 R−/− compared to CCK1 R+/+ mice. However, meal size was larger in the CCK1 R−/− mice compared to CCK1 R+/+ mice when fed a HF diet, with a concomitant decrease in meal frequency. Meal duration was increased in mice fed HF diet regardless of phenotype. In addition, CCK1 R−/− mice fed a HF diet had a 75% decrease in the time to 1st meal compared to CCK1 R+/+ mice following a 6 h fast. These data suggest that lack of the CCK1 R results in diminished satiation, causing altered meal patterns including larger, less frequent meals when fed a high fat diet. These results suggest that the CCK1 R is involved in regulating caloric intake on a meal to meal basis, but that other factors are responsible for regulation of daily food intake.