Figure 4.

Indirect calorimetry and metabolic cage analysis. Following a 48 h habituation period, mice (n = 4 from each study arm indicated) were monitored over a 24 h period. Data are mean ± SEM from eight-month-old mice. ((A)—Respirometry) As demonstrated by the positive mean differences, in the light, dark, and overall (total), vehicle-treated Agl^−/− mice demonstrate lower respiratory exchange ratio (RER, (A1)), total energy expenditure (TEE, (A2–A4)), and carbohydrate oxidation (A6). As shown by the negative mean differences, fat oxidation was reduced in Agl^−/− mice in light, dark, and overall as compared to WT mice (A5). All these parameters were increased or corrected by GHF-201 at all times, except for fat oxidation in the dark and overall (A4). ANCOVA results suggest that weight-dependent TEE is reduced in Agl^−/− compared to WT mice in both the light condition (A2) and overall (A4), and that GHF-201 corrects this TEE reduction in Agl^−/− mice in the light. ((B)—Activity) Ambulatory activity (B1) and wheel running (B2) were also increased (corrected), or not affected, by GHF-201 as indicated. ((C)—Food and Water Intake) Food intake (C1) was not significantly affected, and water intake ((C2), total cumulative values are shown in the bar graphs) was increased, mainly in the dark period, by GHF-201. Statistical significance of mean differences was determined by One Way ANOVA with repeated measures with a Tukey post hoc test. *, 0.01 < p < 0.05; **, 0.001 < p < 0.01; ***, p < 0.001; ****, p < 0.0001; ns, non-significant.