We further observe that obesity-repressed LincIRS2 is negatively controlled by MAFG and CRISPR–Cas9-mediated knockout, or antisense-mediated RNA interference of LincIRS2 causes hyperglycemia, insulin resistance, likely caused by alterations in glucogenic gene expression in lean mice. The gene discussed is MAFG; the disease is obesity due to melanocortin 4 receptor deficiency.