iSIRT3 and S3fl control mice had similar body weight, body composition, energy intake, and whole body energy metabolism. (A) Body weights of iSIRT3 and S3fl mice on control diet (CD) or high-fat diet (HFD) monitored over time. [n = 8–10; 3-way RM ANOVA (time × diet × genotype), time × diet, P < 0.0001: followed by a restricted 2-way ANOVA (diet × genotype) at each time point; diet, #P < 0.0001. (B) CT scan analyses of S3fl and iSIRT3 mice fed CD or HFD. [n = 6–8; 2-way ANOVA (diet × genotype) with Tukey's multiple comparisons post hoc test. For lean mass, fat mass, visceral fat, and subcutaneous fat; diet effects, ∗P < 0.05, #P < 0.0001. Subcutaneous fat; diet × genotype, $P < 0.05]. (C–F) Indirect calorimetry data. The grey and white bars in the background represent the dark and light phases, respectively. (C) Energy intake measured every 12 h. (D) Respiratory exchange ratio (RER) (E) Locomotor Activity and (F) Energy expenditure (EE) values plotted as mean values of 1 h time bins. (C–F) [n = 8–9; mixed RM ANOVA (genotype × diet × days × phases) with measurements over time compacted into diet (CD and HFD), days (day 1 and 2) and phases (dark and light)]. Data are presented as mean values ± SEM.