Selective overexpression of MRAP2 in the PVN MC4R neurons affects metabolism in female mice. (A–C) Graphs showing body weight (A), fat mass (B), and lean mass (C) of Mc4r-crePVN-GFPcontrol female mice (n = 11) and Mc4r-crePVN-MRAP2 (n = 11) female mice at 4, 8 and 12 weeks after injection. (D and E) Graphs showing food intake in Mc4r-crePVN-GFP female mice (n = 8) and Mc4r-crePVN-MRAP2 female mice (n = 10). Total cumulative food intake in the 24 h cycle is shown (D) and in the dark and light phases of the cycle (E). Gray area in D represents the dark phase. (F–I) Graphs showing locomotor activity (F) and total energy expenditure in the 24-h period (G) and in the dark (H) and light (I) phases of the cycle of Mc4r-crePVN-GFP (n = 8) and Mc4r-crePVN-MRAP2 mice (n = 10) three months after the PVN viral injections. (J–L) Graphs showing O2 consumed (J), CO2 produced (K), and the ratio in (L) of Mc4r-crePVN-GFP (n = 8) and Mc4r-crePVN-MRAP2 mice (n = 10) three months after the PVN viral injections. All data are presented as mean ± SEM. *P < 0.05; **P < 0.01; ***P < 0.001 compared to Mc4r-crePVN-GFP mice.