In the converse genetic manipulation, reduced Ins2 dosage (on an Ins1-null background) led to high-fat fed female Ins1-/-:Ins2+/- mice having lower insulin secretion than their Ins1-/-:Ins2+/+ controls at a young age, which again corresponded with attenuated obesity [19]. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.