Besides, chronic HFD exposure often fires “multiple hits” in the liver, resulting in impaired insulin response cascades and leading to insulin resistance, which has become an important complication and diagnostic index of NAFLD.33 In this regard, after Zbtb18 overexpression we also found a glucose intolerance improvement and a reduced insulin resistance, coupled with an enhanced phosphorylation of AKT and GSK-3β in the liver. This evidence concerns the gene AKT1 and metabolic dysfunction-associated steatotic liver disease.