(A and B) Food intake increased the percentage of PrRP neurons expressing p-CREB (A; n = 7 or 9) and the number of Fos-positive PrRP neurons (B; n = 7 or 8) in the rat NTS. Photographs show PrRP neurons (brown cytoplasmic reactions) in the NTS. A dark nuclear reaction indicates p-CREB immunoreactivity. Scale bar: 30 μm. (C) Food intake after a 24-hour fast in WT and PrRP-deficient mice at the age of 14 weeks. Food intake was greater in PrRP-deficient mice (n = 9 or 10). (D) Cumulative food intake of WT and PrRP-deficient mice at the age of 24 weeks. PrRP-deficient mice ate more food (n = 8). (E–H) Cumulative food intake of rats injected i.c.v. with anti-PrRP mAb or mouse IgG at the beginning of the dark period (E and G) or 3 hours after the beginning of the light period (F and H). Rats in G and H were fasted before the i.c.v. injection (n = 8 or 9). (I and J) Meal size but not meal frequency was greater in PrRP-deficient mice (14 weeks old; n = 6 or 10) or rats injected i.c.v. with anti-PrRP mAb (10 weeks old; n = 8) than in control WT mice or control rats. (K) Cumulative food intake of WT mice or PrRP-deficient mice injected i.p. with CCK at the age of 19–21 weeks. Suppression of food intake by CCK was blocked in PrRP-deficient mice (n = 6 or 7). The intake ratio of high-fat diet (L) or tallow (M) was not significantly different in WT and PrRP-deficient mice at the age of 34–37 weeks (n = 4). Error bars indicate SEM. ^†P < 0.05, ^‡P < 0.01, ^#P < 0.001 versus WT mice; *P < 0.05, ***P < 0.001 versus fasted rats, mouse IgG-injected rats, or vehicle-injected mice. HC, high-carbohydrate diet.