The nocturnal

and diurnal data were analyzed separately to distinguish between periods of low (diurnal) and high (nocturnal) physical activity. The total energy expenditure was similar across all dietary intervention groups (Fig. 3A). For food intake, no significant differences were observed between the groups (data not shown). Despite similarities in total energy expenditure and food intake, the HFD-fed mice supplemented with META060 or rosiglitazone exhibited a significantly lower mean nocturnal FA oxidation rate than the HFD-only group (0.16 ± 0.01 and 0.18 ± 0.01 versus 0.22 ± 0.01 kcal/h, P < 0.001 and P < MS-275 ic50 0.01, respectively), and rosiglitazone had a lower mean diurnal FA oxidation rate compared with the control group (0.12 ± 0.01 versus 0.15 ± 0.01 kcal/h, P < 0.05; Fig. 3B). In addition, the nocturnal CHO oxidation levels were increased in the HFD-fed mice that received META060 or rosiglitazone compared with controls (0.36 ± 0.02 and 0.35 ± 0.01 versus 0.31 ± 0.01 kcal/h, P < 0.01; Fig. 3C). This increased CHO-to-fat oxidation ratio was reflected SB203580 mouse in the RER. META060 and rosiglitazone significantly increased the RER in HFD-fed mice during the diurnal period compared with the HFD-only–fed mice (0.88 ± 0.00 and 0.89 ± 0.01 versus 0.86 ± 0.01, P < 0.05 and P < 0.01, respectively) and during the nocturnal period (0.87 ± 0.01 and 0.86 ± 0.00 versus 0.83 ± 0.01, P < 0.001, respectively;

Fig. 4A, B). To test the ability of the animals to adjust the fuel oxidation to fuel mafosfamide availability (metabolic flexibility), the animals were fasted overnight; subsequently, the food was

replaced and the RER was monitored. The META060- and rosiglitazone-supplemented mice had a significantly higher RER when the food was replaced compared with the HFD-only–treated mice (0.94 ± 0.00 and 0.94 ± 0.00 versus 0.92 ± 0.00, P < 0.001), indicating greater metabolic flexibility in the META060- or rosiglitazone-fed animals ( Fig. 4C). Physical activity measurements did not show differences in either treatment group compared with the HFD-only–fed mice (data not shown). Because META060 decreased fat oxidation, we investigated whether fat absorption was impaired in the META060-supplemented mice. The fecal FA composition and concentration were determined in samples collected during metabolic cage experiments (data not shown). No difference was found in total fecal weight. Furthermore, the quantitative gas chromatographic analysis showed equal fecal FA composition and fecal FA content in all treatment groups. Together with the equivalent food intake, this implies a similar intestinal absorption of lipids. Because an increased CHO-to-fat oxidation ratio and an increased metabolic flexibility suggest protection against HFD-induced insulin resistance, oral glucose tolerance tests were performed during week 5 of the dietary intervention.