Sesn2 knockout aggravates glucose intolerance, insulin resistance, hepatocyte apoptosis, macrophage infiltration, and hepatic stellate cells (HSCs) activation in wild-type C57BL/6 J mice fed with high-fat diet (HFD) or in Lepob/ob mice, which involves AMPK inhibition and mTORC1-S6K activation; Ectopic SESN2 reconstitution can rescue SESN2-deficient mice from HFD-caused liver damage [60, 90]. This evidence concerns the gene SESN2 and Insulin resistance.