Thus, only after this concurrent salutary activation of the adiponectin-LKB1-AMPK-FOXO-signaling axis wanes (Fig. 7D), do these CHIP−/−-mice begin to show characteristic NASH symptoms i.e. macrovesicular steatosis and marked hepatocellular ballooning. This evidence concerns the gene PRKAA2 and metabolic dysfunction-associated steatohepatitis.