While data from the present study show that GPRKO female mice fed the HFD displayed better insulin sensitivity and glucose homeostasis, these beneficial effects may be the secondary effects whereby deletion of GPR30 prevented obesity in mice fed a HFD, given that deletion of GPR30 had no effects on blood glucose, insulin, and insulin sensitivity in STD-fed mice. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.