The original uncropped blot images.

<div><p>Obesity is associated with abnormal repolarization manifested by QT interval prolongation, and oxidative stress is an important link between obesity and arrhythmias. However, the underlying electrophysiological and molecular mechanisms remain unclear. The aim of this study is to evaluate the role of obesity in potassium current in ventricular myocytes and the potential mechanism of NADPH oxidase 2 (Nox2). We investigated the effect of Nox2 on cardiac repolarization without compromising its expression and function in other systems using mice with conditional cardiac-specific deletions of Nox2 (knockout [KO]). Wild-type, KO, and Flox littermate mice were randomized to either the control or high-fat diet (HFD) groups. Surface electrocardiograms were recorded to analyze repolarization in vivo. Whole-cell patch-clamp techniques were used to evaluate the electrophysiological phenotype of isolated myocytes in vitro. Western blotting was performed to assess protein expression levels. Compared with the control mice, the HFD group had a prolonged QTc. The consequences of an HFD were not attributed to delayed rectifier K<sup>+</sup> and inward-rectifier K<sup>+</sup> currents but were associated with reduced peak outward K<sub>V</sub> and fast transient outward K<sup>+</sup> currents. Downregulated expression of K<sub>V</sub>4.2 and KChIP2, comprising functional I<sub>to</sub> channel pore-forming (α) and accessory (β) subunits, was detected in HFD mice. Nox2-KO reversed the effect of obesity on I<sub>peak</sub> and I<sub>to</sub> amplitude. Our data demonstrate that obesity mediates impaired cardiac repolarization in mice, manifested by QTc at the whole organism level and action potential duration at the cellular level, and correlated with Nox2. The electrophysiological and molecular aspects of this phenomenon were mediated by repolarizing outward K<sup>+</sup> currents.</p></div>