Obese male mice (ob/ob) are normally sensitive to the satiating effect of CCK-8.

The ob/ob mouse has a defect in short-term satiety mechanisms because ob/ob mice eat larger meals than leans and have abnormal postprandial behaviors. We suggested that this defect involved a failure to release CCK normally in response to ingested nutrients and/or decreased receptor sensitivity to CCK. McLaughlin and Baile reported that female obese mice were less sensitive to the satiating effect of CCK-8, a result consistent with the hypothesis of decreased receptor sensitivity. To investigate this possibility further, we determined the sensitivity to exogenous CCK-8 of obese and lean male mice. Adult male C57Bl/6J ob/ob and male +/+ controls were injected with CCK-8 (1, 2, 4, and 8 micrograms/kg, IP) 15 min prior to the presentation of solid food (Noyes pellets) after 4.5 hr food deprivation in the dark. Food intake (FI) was measured at 30 min and 150 min. CCK-8 decreased FI during the first 30 min in both obese and lean mice (p less than 0.01). The threshold dose for inhibition of FI was 2 micrograms/kg in obese and 4 micrograms/kg in lean. Since obese mice weighed approximately twice as much as lean mice, their total dose of CCK-8 was equal to that of lean mice. Thus, obese male mice were at least as sensitive to the satiating effect of CCK-8 as lean male mice. These results do not confirm McLaughlin and Baile's result in female mice eating in the light and they suggest that the defect in satiety in obese male mice is not the result of decreased sensitivity of CCK receptors.