Prevented NASH development as well as ameliorated established NASH and fibrosis without affecting total calorie intake and metabolome analyzes identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. Here, PCK1 is linked to metabolic dysfunction-associated steatohepatitis.