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. 2019 Feb 5;22:49–61. doi: 10.1016/j.molmet.2019.01.013

Figure 1.

Figure 1

The Pnpla3 ASO treatment reduced liver Pnpla3 mRNA and protein levels in both Pnpla3 mutant knock-in mice and wild-type littermates fed a high-sucrose diet but reduced hepatic triglyceride content only in mutant mice. A total of 21 female homozygous Pnpla3 148M/M knock-in mice and 19 wild-type littermates were fed a high-sucrose diet for 15 weeks. After 7 weeks of feeding on the high-sucrose diet, mice were assigned to ASO study groups based on body weight and liver fat percentage, as assessed by MRI. Pnpla3 mutant knock-in and wild-type mice were treated with either the control or Pnpla3 ASO (5 mg/kg/week administered by two subcutaneous injections per week, n = 9–12 mice/group) for 8 weeks. (A) Body weight gain before and after the ASO treatment. (B) Caloric intake before and after the ASO treatment. (C) Liver Pnpla3 mRNA levels were measured by qPCR and normalized to the ribosomal protein large P0 (Rplp0). (D) Levels of the Pnpla3 protein in hepatic lipid droplets were measured by western blotting. Plin2 was used as the loading control. Hepatic lipid droplets where purified by density gradient ultracentrifugation (see the Materials and Methods). (E,H) Representative images of Oil Red O-stained liver sections after 8 weeks of ASO treatment (black scale bar represents 100 μm). Liver lipid levels were assessed by MRI after 6 weeks of ASO treatment, and liver and plasma triglyceride levels were measured by biochemical assays when Pnpla3 mutant knock-in (F–G) and wild-type (I–J) mice were euthanized after 8 weeks of ASO treatment. Values are presented as the mean ± SEM. P values were calculated using 2-sided t-tests. Abbreviations: ASO: antisense oligonucleotide; MRI: magnetic resonance imaging; Plin2: perilipin 2; Pnpla3: patatin-like phospholipase domain-containing 3; Rplp0: ribosomal protein large P0; AU: arbitrary unit; Ctrl: control. 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.