Summation of the results further indicate that increased oxidative stress and hepatocellular apoptosis, inactivation of Akt and AMPK, and activation of its downstream targets SREBP-1 and ACC, together with stimulation of ERK are involved in the pathogenesis of nicotine plus HFD-induced hepatic steatosis. The gene discussed is PRKAA2; the disease is Hepatic steatosis.