CCK(1) receptor is essential for normal meal patterning in mice fed high fat diet.

Cholecystokinin (CCK), released by lipid in the intestine, initiates satiety by acting at cholecystokinin type 1 receptors (CCK(1)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 CCK(1)R in the short term effects of a high fat diet on daily food intake and meal patterns using mice in which the CCK(1)R gene is deleted. CCK(1)R(-/-) and CCK(1)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 CCK(1)R(-/-) compared to CCK(1)R(+/+) mice. However, meal size was larger in the CCK(1)R(-/-) mice compared to CCK(1)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, CCK(1)R(-/-) mice fed a HF diet had a 75% decrease in the time to 1st meal compared to CCK(1)R(+/+) mice following a 6 h fast. These data suggest that lack of the CCK(1)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 CCK(1)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.