A hepatocyte NAFLD model has shown that oxidative stress triggers the activation of a G2/M DNA damage checkpoint, preventing the activation of the cyclin B1/CDK1 complex, which causes an inefficient progression through the S/G2 phases, suggesting that polyploidy in mononuclear cell populations is an early event in NAFLD development [11]. This evidence concerns the gene CDK1 and metabolic dysfunction-associated steatotic liver disease.