Increased blood glucose with elevated serum insulin and systemic oxidative stress in HFHSD‐fed LE2KO (A, B) Fasting blood glucose (A) (controls on NC; n=9, LE2KO on NC; n=9, controls on HFHSD; n=10, LE2KO on HFHSD; n=10) and serum insulin levels (B) (controls on NC; n=9, LE2KO on NC; n=9, controls on HFHSD; n=12, LE2KO on HFHSD; n=12) in controls and LE2KO fed NC or HFHSD, respectively. (C, D) Measurements of ROM (C), a systemic oxidative stress marker (n=10 for each group), and BAP (D), an indicator of antioxidant capability (controls on NC; n=10, LE2KO on NC; n=10, controls on HFHSD; n=8, LE2KO on HFHSD; n=8). Error bars represent SEM. *P<0.05, **P<0.01 vs. controls fed HFHSD. BAP indicates biological antioxidant potential; ERK, extracellular signal‐regulated kinase; HFHSD, high‐fat/high‐sucrose diet; LE2KO, liver/specific ERK2 knockout mice; NC, normal chow; ROM, reactive oxygen metabolites.