Full food deprivation-induced activation of PVHCRF neurons requires a decrease of the plasma LEAP2 levels. A Quantitative analysis of the mean intensity of the CRF + signal in the PVH of WT mice SC-treated with vehicle- or LEAP2(1−12) in each experimental group. Two-way ANOVA detected significant condition x treatment interaction: P = 0.0094, F (1,15) = 8.874. B Percentage of CRF + cells positive for c-Fos in the PVH of WT mice SC-treated with vehicle- or LEAP2(1−12) in each experimental group. Two-way ANOVA detected significant condition x treatment interaction: P = 0.0463, F (1,15) = 4.716. C Plasma corticosterone levels of WT mice SC-treated with vehicle- or LEAP2(1−12) in each experimental group. Two-way ANOVA revealed no condition x treatment interaction, but a main effect of both condition: P < 0.0001, F (1,20) = 179.8, and treatment: P = 0.0254, F (1,20) = 5.831. D Plasma glucose levels of WT mice SC-treated with vehicle- or LEAP2(1−12) in each experimental group. Two-way ANOVA revealed no condition x treatment interaction, but a main effect of condition: P < 0.0001, F (1,20) = 34.57. Bars indicate mean ± SEM. Circles represent individual values. Tukey’s multiple comparisons test shows significant differences between ‘condition’ and ‘treatment’. *p < 0.05, **p < 0.001, ***p < 0.001 and ns not significant