Therefore, the observation that an interplay among HMGA1 and FoxO1 can be a component of the insulin/FoxO1 signaling pathway constitutes a novel point of the present study, which may help in understanding the molecular basis of certain disorders where insulin action becomes compromised (e.g. obesity, type 2 diabetes and other insulin-resistant conditions). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.