The Pnpla3 ASO treatment improved liver steatosis score, lobular inflammation score, NAFLD activity score, and fibrosis stage in Pnpla3 mutant knock-in mice and steatosis score and NAFLD activity score in wild-type mice fed a NASH-inducing diet. Homozygous Pnpla3 mutant knock-in and wild-type littermates were fed a NASH-inducing diet for 26 weeks. After 12 weeks of consuming the NASH diet, Pnpla3 mutant knock-in and wild-type mice were treated with either control or Pnpla3 ASOs (5 mg/kg/week administered by two subcutaneous injections per week, n = 8–9 mice/group) for 14 weeks. Liver steatosis score, lobular inflammation score, NAS, and fibrosis stage in Pnpla3 mutant knock-in (A) and wild-type (B) mice. P values were calculated using ordinal regression analyses. Abbreviations: NAS: NAFLD activity score: Pnpla3: patatin-like phospholipase domain-containing 3. Mutant knock-in mice are defined as homozygotes for a methionine (M) at position 148 of the Pnpla3 protein, while wild-type littermates are homozygotes for an isoleucine (I) at the same position. WT: wild-type; MUT: mutant.