Collectively, these data favor arole for NADPH oxidase, O2− generation, Akt, eNOSand the stress signaling molecules p38, JNK and NFκB, rather than Ob-R andSTAT-3, in the basal and leptin-elicited cardiac response during aging and obesity.Our data further revealed both similarity and disparity in aging-associatedcardiomyocyte mechanical response between ob/ob obesity and highfat diet-induced or the hyperleptinemic db/db obesity. The gene discussed is AKT1; the disease is obesity due to melanocortin 4 receptor deficiency.