From a mechanistic point of view, it has been proposed that the insulin receptor substrate-1 (IRS-1)/PI3K/Akt pathway seemed to be inversely correlated to the pathogenesis of NAFLD, since knockout of IRS-1 [103] and recovery of the PI3K/Akt activity [104] protects the liver from NASH-induced injury. This evidence concerns the gene AKT1 and metabolic dysfunction-associated steatotic liver disease.