HFHS diet causes hyperphagia and weight gain in CCK‐SAP‐treated rats. Rats received bilateral NG injection of SAP (400 ng/side) or CCK‐SAP (400 ng/side) and maintained on chow for 11 weeks post‐op before switching to HFHS diet (n = 8/group). A, There was no post‐op body weight gain during 11 weeks on chow, but CCK‐SAP‐treated rats started gaining more weight upon transitioning to HFHS diet (n = 8, two‐way ANOVA, interaction F(16,112) = 2.585, P = .0019, Benjamini, Krieger and Yekutieli post hoc analysis with FDR 0.05, *P < .05, †
P < .01). B, Normalizing weight gain to the body weight upon dietary switch, confirms greater weight gain in CCK‐SAP‐treated rats compared to SAP controls (n = 8, two‐way ANOVA, interaction F(5,60) = 3.381, P = .0093, Holm Sidak post hoc analysis, *P < .05, †
P < .01). C, Weekly food intake remained similar between groups for the rats on chow for 11. Caloric intake increased in response to HFHS diet in both groups compared to chow (n = 8, two‐way ANOVA, interaction F(15, 210) = 4.457, P < .0001, Benjamini, Krieger and Yekutieli post hoc analysis, *P < .05, †
P < .01). D, Caloric intake was greater in CCK‐SAP‐treated, compared to SAP‐treated, rats (n = 8, two‐way ANOVA, interaction F(4,52) = 2.176, P = .0845, Holm Sidak, different lettersa,b indicate P < .05). E‐F, Analysis of age‐matched 6 weeks post‐surgery of bilateral SAP or CCK‐SAP in NG on respective diets. E, HFHS diet increases body weight gain more rapidly in CCK‐SAP‐treated compared to SAP‐treated rats (n = 7‐14, two‐way ANOVA, interaction F(15,165) = 10.53, P < .001, Holm‐Sidak post hoc analysis, *P < .05, †
P < .01, ‡
P < .001 compared to chow, and ζp < 0.01 compared to SAP‐HFHS group). F, HFHS‐fed CCK‐SAP‐treated rats consume more calories per week than all other groups at time point, while HFHS‐fed SAP‐treated rats normalize intake compared to chow‐fed rats in the last 3 weeks of the study (n = 7‐14, two‐way ANOVA, interaction F(15,165) = 10.53, P < .001, Holm‐Sidak post hoc analysis, different lettersa,b,c indicate P < .05 between groups)