To this extent, modified and optimized antisense oligonucleotides have been utilized to enhance both liver and peripheral insulin function for the selective suppression of FoxO1 expression (FoxO1-antisense oligonucleotide treatment) by reducing the plasma glucose amount and elementary endogenous glucose production rate in mice with diet-associated obesity [96,97]. This evidence concerns the gene FOXO1 and obesity due to melanocortin 4 receptor deficiency.