The results of the present work demonstrate negative transcriptional regulation of the IFNG gene in adipose and immune tissues in animals supplemented with TetraSOD®, together with the parallel expression profiles observed for other genes encoding key cytokines regulating the inflammatory response, such as IL-1β and TNF-α, strengthening the relevance of TetraSOD® as a dietary supplement to control and modulate the inflammatory status associated with obesity and MetS. This evidence concerns the gene IFNG and obesity due to melanocortin 4 receptor deficiency.