To obtain mechanistic insights into the improved metabolic profiles and to assess the cause of lower body weight in FoxO1 KODAT mice especially under HFD challenge, we analysed food intake, energy expenditure and physical activity of the HFD-fed mice using metabolic chambers. To rule out secondary metabolic effects of body weight difference, mice fed on HFD for 1 week with comparable body weight were used (Supplementary Fig. 2l). Although there was a minor trend towards an increase in HFD intake, the FoxO1 KODAT mice showed no significant difference in total accumulated food intake (Fig. 5a). In addition, physical activity of FoxO1 KODAT mice (either inside or outside of the metabolic chambers) was similar to WT controls (Fig. 5b and Supplementary Fig. 4a). In contrast, measurements of respiratory exchange demonstrated an increase in O2 consumption and CO2 production in KO mice (Fig. 5c–f). Moreover, FoxO1 KODAT mice showed robustly increased heat generation compared with WT littermates (Fig. 5g). In line with the increased energy expenditure, the rectal temperature of KO mice was higher than that of WT controls (Fig. 5h). These
