In addition, Sun et al. (10) reported an increase in Akt phosphorylation with resveratrol in C2C12 cells initially treated with lipid to induce insulin resistance; however, in our insulin-resistant individuals with severe obesity, we did not observe improvements in the insulin-signaling cascade, which suggests that the resveratrol-mediated mechanisms involved in improving insulin action may differ between lipid exposure and tissue that is intrinsically insulin resistant. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.