Nevertheless, numerous studies have found exogenous administration of IL-22 in leptin-deficient and HFD feed mice reverses many symptoms of the metabolic syndrome, suppresses ER stress and inflammation11–13 although a 2015 study showed no effect of IL-22 administration or IL-22 genetic deletion on HFD-induced obesity and insulin resistance14. This evidence concerns the gene IL22 and obesity due to melanocortin 4 receptor deficiency.