HFHSD‐fed LE2KO demonstrate increased aortic superoxide production and aortic H2O2 release accompanied by elevated Nox1 and Nox4 gene expressions. (A, B) DHE staining of liver sections (A) and quantification of DHE fluorescence intensity (B) in controls and LE2KO on NC or HFHSD, respectively (controls on NC; n=5, LE2KO on NC; n=5, controls on HFHSD; n=6, LE2KO on HFHSD; n=6). (C) Measurements of aortic H2O2 release in controls and LE2KO on NC or HFHSD, respectively (n=8 for each group). (D‐H) mRNA expressions of Nox1, Nox2, Nox4, SOD1 and SOD3 aortas from controls and LE2KO on NC or HFHSD, respectively (n=5 for each group). Error bars represent SEM. *P<0.05, **P<0.01, ***P<0.001 vs. controls fed HFHSD. DHE indicates dihydroethidium; ERK, extracellular signal‐regulated kinase; HFHSD, high‐fat/high‐sucrose diet; LE2KO, liver‐specific ERK2 knockout mice; NC, normal chow; Nox, nicotinamide adenine dinucleotide phosphate oxidase.