Consistent with previous studies (32, 41–43), male mice fed HFD for 16 weeks presented with obesity, hyperglycemia, glucose intolerance, insulin resistance, defective glucose-stimulated insulin release (GSIS), and changes in islet gene expression such as Ins1, Ins2 and Gck (Figure S1B–H), as expected. This evidence concerns the gene GCK and obesity due to melanocortin 4 receptor deficiency.