Figure 6.

PrRP Neurons in the Hypothalamus Mediate the Thermogenic Action of Leptin, while PrRP Neurons in the Brainstem Mediate the Anorectic Action of CCK

(A) Growth curves of wt, nestin-Cre, LSL-PrRP, and nestin-Cre::LSL-PrRP littermates. LSL-PrRP, which lack universal expression of PrRP, are obese, whereas nestin-Cre::LSL-PrRP mice, which have PrRP rescued in the brain, are not.

(B) Growth curves of wt, TH-Cre, LSL-PrRP, and TH-Cre::LSL-PrRP littermates. TH-Cre::LSL-PrRP mice, which have PrRP rescued only in neurons of the NTS and VLM, do not become obese. (n = 5 to 6 per group, bars represent mean ± SEM; two-way ANOVA repeated-measures, ^∗p < 0.05; ^∗∗∗p < 0.001). (For validation of the rescue of PrRP expression in the two Cre crosses, see Figure S5).

(C and E) Leptin administration (5 mg/kg, i.p.) acutely increases body temperature in wt and mice expressing PrRP in the brain (nestin-Cre::LSL-PrRP) (n = 6–8 per group, bars represent mean ± SEM; two-way ANOVA, ^∗∗∗p < 0.001).

(C, D, and F) Leptin administration (5 mg/kg, i.p.) acutely increases body temperature in wt but not mice expressing PrRP selectively in the brainstem (TH-Cre::LSL-PrRP) (n = 6 to 7 per group, bars represent mean ± SEM; two-way ANOVA, ^∗∗∗p < 0.001). Dotted line in (C) and (D) represents time of injection.

(G and H) The anorectic action of leptin (2 hr food intake) (G) in mice expressing PrRP in the brain (nestin-Cre::LSL-PrRP), and (H) in mice expressing PrRP in brainstem neurons only (TH-Cre::LSL-PrRP). (5 to 6 weeks old, n = 5 to 6 per group, bars represent mean ± SEM; two-way ANOVA, ^∗p < 0.05, ^∗∗p < 0.01).

(I and J) The anorectic actions of CCK (1 hr food intake) (I) in mice expressing PrRP in the brain (nestin-Cre::LSL-PrRP), and (J) in mice expressing PrRP in brainstem neurons only (TH-Cre::LSL-PrRP). (5 to 6 weeks old, n = 5 to 6 per group; bars represent mean ± SEM; two-way ANOVA, ^∗p < 0.05; ^∗∗p < 0.01; ^∗∗∗p < 0.001.)