Its hepatic knockout leads to upregulated activity of the downstream ISR signalling protein, ATF4 and its target genes ASNS, ATF5 and FGF21. Additional results based on further knockout mice models suggested that liver activation of IRS may be a viable target to treat obesity through the upregulation of FGF2167,68. The gene discussed is ATF5; the disease is obesity due to melanocortin 4 receptor deficiency.