IRS1 and Insulin resistance: While downregulation of Irs2 accompanied by decreased gluconeogenic gene expressions was observed in both patients with simple steatosis and NASH, expression of FAS, a lipogenic gene, was not decreased and was strongly correlated with Irs1 expression in NAFLD, suggesting that selective insulin resistance via downregulation of Irs2 is present in the early stages of NAFLD in humans [165].