Although it has been previously shown that Sirt3 loss in mice on a high-fat diet accelerates obesity, insulin resistance, hyperlipidemia, and steatohepatitis (39), and SIRT3 preserves heart function and capillary density (40), our results show that Sirt3 loss increases survival and decreases tumor incidence upon HFD. Here, SIRT3 is linked to Insulin resistance.