Mice were fed the HF/HC diet for 16 weeks. During the sixteenth week glucose or pyruvate tolerance test was performed. At the time of sacrifice, blood was drawn for insulin and glucose determinations. (A,B) Blood insulin levels and HOMA-IR. (C,D) Blood glucose at indicated times after glucose or pyruvate challenge. (E) DHE-stained liver sections (×20 magnification) and (F) ImageJ quantification demonstrating increased oxidative stress in chow-fed ALR-H-HET and ALR-H-KO mice, which increases greatly after HF/HC feeding. (G) 4HNE-stained liver sections (20× magnification) and (H) ImageJ quantification demonstrating much increased oxidative stress in chow-fed ALR-H-KO mice; 4HNE staining increased in all mice after HF/HC feeding, the magnitude being greater in ALR-H-HET and ALR-H-KO mice. (I) Malondialdehyde quantification showing already increased peroxidation in chow-fed ALR-H-HET mice compared to WT mice, which increased further after HF/HC feeding. Basal hepatic lipid peroxidation is much greater in ALR-H-KO mice and does not change after HF/HC feeding. (J) Hepatic GSH concentration in chow-fed or HF/HC-fed WT, ALR-H-HET and ALR-H-KO mice. Abbreviations: FU, fluorescence unit; GSH, glutathione; HPF, high-power field; MDH, malondialdehyde.