Stk25-targeting ASOs efficiently suppressed oxidative stress and improved mitochondrial activity in the livers of obese mice. Mice were treated with GalNAc-Stk25 ASO (12.5 mg/kg/wk), Stk25 ASO (50 mg/kg/wk), GalNAc-control ASO (12.5 mg/kg/wk), or placebo (PBS) for 6 weeks. (A) Representative liver sections processed for immunohistochemistry/immunofluorescence with anti–4-HNE (brown) or anti-PEX5 antibodies (green), or stained with DHE (red) or MitoTracker Red (red); nuclei were stained with DAPI (blue). Scale bars: 50 μm for 4-HNE, DHE, and MitoTracker Red, and 12.5 μm for PEX5. (B and D) Quantification of (B) 4-HNE adducts and (D) TBARS in liver extract. (C, E, and F) Quantification of (C) DHE, (E) MitoTracker Red, and (F) PEX5 staining. (B–F) Data are means ± SD from 6–8 mice per group. Cntr, control. *P < .05, **P < .01, BP = .087.