reported that suppression of islet NPY and Y1 receptor mRNA expressions was associated with increased islet insulin secretion in HFD-fed C57BL/6 mice and leptin-deficient ob/ob mice [12], thus linking the reduced islet NPY-Y1 signaling to the natural course of β-cell compensation during obesity. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.