The administration of Exendin-4 and CCK affects food intake differentially in female and male rats tested on an alternate day fasting paradigm.

Alternate day fasting (ADF) which involves the repetition of a 2-day cycle of a day of free access to food followed by a day of limited or no access to food, is an effective dietary intervention for weight loss in both humans and rats. We have previously reported that when presented with a high energy (HE) and standard chow diet, rats maintained on an ADF schedule displayed decreased HE diet preference compared to controls. Both male and female ADF rats increased overall intake of chow. However, this increase was driven by both meal size and meal number for males and only number of meals for females. Administration of cholecystokinin (CCK) or the glucagon-like peptide 1 (GLP-1) receptor agonist Exendin-4 (Ex-4) reduces food intake. It appears that CCK decreases food intake primarily through satiety signals whereas GLP-1 signaling may reduce intake by satiety and reward cues. Here, female and male rats were administered (i.p.) saline, 3.0 µg/kg Ex-4 (3 h before test), 3.0 µg/kg CCK (15 min before test) or a combination of both. Next, all rats were presented 23-h access to both HE diet and chow following food-restriction (ADF) or free access to chow (CON). Compared to saline-control sessions, administration of the combination of Ex-4 and CCK, but not Ex-4 or CCK alone, resulted in a decrease in both HE and chow intake early in the session for male ADF rats but the combination primarily decreased chow diet intake early in the session for female ADF rats. Thus, it appears that under these energy homeostatic conditions, administration of Ex-4 or CCK alone does not affect intake in ADF rats, but the combination produces decreases in feeding that are more than the sum of their individual effects. These findings support a role for the combination of GLP-1 and CCK signaling in the changes in diet preference induced by an alternate day fasting paradigm differentially in female and male rats.