Sirt6 ablation mediated by ap2-CRE or adiponectin-CRE in adipose tissue increased HFD-induced obesity and insulin resistance (Kuang et al., 2017; Yao et al., 2017), and Sirt6 overexpression inhibited HFD-induced obesity and insulin resistance (Kanfi et al., 2010). Here, SIRT6 is linked to obesity due to melanocortin 4 receptor deficiency.