Moreover, our in-vitro and in-vivo studies confirmed that the increase in adipose tissue-derived microRNA-450a-5p after obesity could inhibit the JNK/IRS/PI3K/AKT activity via DUSP10 in the liver and adipose tissue; thus, impairing glucose tolerance and promoting the occurrence of IR, and targeted inhibition of microRNA-450a-5p could effectively improve T2DM symptoms. The gene discussed is MAPK8; the disease is obesity due to melanocortin 4 receptor deficiency.