Schematic of the study design: mc4r−/−mice fed a HFD pairfat to WT-DIO mice for 16 weeks, after which they were treated with 14-day daily 2 mg/kg RAP i.p. injections followed by another 14-day daily i.p. VEH injections. Both groups of mice had ad libitum access to HFD throughout the pharmacological treatment. Schematic diagram of testing diet-dependent effects of RAP in HFD-mc4r−/−obese mice. Pairfat mc4r−/−and WT-DIO mice were treated with daily i.p. injections of RAP (2 mg/kg) for 14 days while ad libitum-fed on HFD.