INSR and obesity due to melanocortin 4 receptor deficiency: Thus, subjects with the MTHFR 677TT or MTRR 66AG/GG genotypes, who were genetically predisposed to HHcy and subsequent insulin resistance, might be more susceptible to the suppression effect of being overweight/obesity on insulin receptor signaling, whereas this effect is not seen in individuals whose weight is in the normal range.