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. The gene discussed is ZBTB18; the disease is metabolic dysfunction-associated steatotic liver disease.