INS and obesity due to melanocortin 4 receptor deficiency: In this study, we avoided the extreme HFD (60% calorie from fat) feeding, which is known to lead to severe obesity, brain insulin resistance, and spatial memory impairment both in AD mouse model and normal C57BL/6 mouse (Ho et al., 2004; Moroz et al., 2008; Barron et al., 2013; Leboucher et al., 2013).