Pharmacological blockade of mitoSTAT3 either by a mitochondrion-targeted STAT3 inhibitor or ROS scavenger concomitantly prevented obesity-associated and fatty acid–induced production of the proinflammatory cytokines IL-17A and IL-6 to indicate a mechanistic link between mitoSTAT3 and inflammatory cytokine production. This evidence concerns the gene IL17A and obesity due to melanocortin 4 receptor deficiency.