Here, we showed that hepatocyte-specific loss of Bach1 improved insulin signaling and dysregulation of glucose homeostasis in HFD-induced hepatic insulin resistance, and consequently protected from HFD-induced steatosis, whereas hepatic overexpression of Bach1 in mice led to the opposite phenotype, indicating that BACH1 is a negative regulator of insulin signaling. The gene discussed is INS; the disease is Insulin resistance.