To explain why Lrp6 haploinsufficiency ameliorated liver injury and reduced the efficacy of silibinin in MCD diet-induced NAFLD, we compared the hepatic expression of Cyp2e1 and the key proteins including Lrp6 and β-catenin, in Wnt/β-catenin signaling between Lrp6(+/-) and Lrp6(+/+) mice received either MCD or MCS diet. This evidence concerns the gene CYP2E1 and metabolic dysfunction-associated steatotic liver disease.