Insulin resistance, a global health threat linked to type 2 diabetes and obesity, can be addressed by modulating the activity of the Sirtuin 1 (SIRT1), a deacetylase that enhances insulin sensitivity by deacetylating the Peroxisome Proliferator‐Activated Receptor Gamma (PPARγ) at lysine 268 and 293. Here, SIRT1 is linked to obesity due to melanocortin 4 receptor deficiency.