Finally, although we did not observe an improvement in glucose tolerance following 16 weeks of HFD in PKR KO mice, plasma insulin levels during the OGTT were significantly lower, indicative of increased insulin sensitivity and consistent with the original report by Nakamura et al. 24 Collectively, the results of previous studies examining the effect of PKR deletion on obesity, glucose metabolism and insulin resistance demonstrate substantial phenotypic variability and, in some instances, relatively modest effects. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.