SIRT6 and obesity due to melanocortin 4 receptor deficiency: Sirt6 overexpression protects against HFD-induced physiological damage by blocking the lipotoxicity of obesity and restoring glucose homeostasis via specific reduction of PPARγ signaling and level of diacylglycerol acyltransferase 1 (DGAT1), a key regulator of TG synthesis (Kanfi et al., 2010).