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. 2023 Aug 9;14:4812. doi: 10.1038/s41467-023-40536-y

Fig. 2. PF-07208254 improves metabolism similar to BT2 and sustainably reduces BCAA and BCKA in mice.

Fig. 2

Mice were fed HFD for 10 weeks, at which time animals were randomized into groups, and treated daily with vehicle, PF-07208254 or BT2. A Study design. B-H Oral glucose tolerance tests (oGTTs) were performed (N = 12 animals/group; a longitudinal mixed effects model with a random intercept and an AR(1) covariance structure was fit for each mouse for the glucose AUCs over the course of the study). B Day 2 oGTT. C Day 2 oGTT AUC. D Week 2 oGTT. E Week 2 oGTT AUC (**p = 0.009, ***p < 0.0001, **p = 0.009). F–H Plasma and livers were isolated 1 h post final compound dose, and steatosis was evaluated by histology (N = 12 animals/group). F Hepatic triglycerides (statistics performed with pairwise Wilcoxon test, ***p = 0.003). G Hepatic steatosis was graded by a veterinary pathologist on a scale of 0-4. (Statistics was performed using a Kruskal Wallis test followed by a Dunn test to compare within groups, ***p = 0.001). H Plasma insulin levels (N = 11–12 animals/group; statistics performed by one-way ANOVA). I, J A PK/PD assessment was performed after 7 weeks of treatment in which mice are dosed with compound, and timed bleeds were performed to measure drug levels, BCAA, and BCKA levels (N = 6–12 animals/group; statistics performed with one-way ANOVA with Tukey HSD test). I Leucine (#p < 0.0001), J Ketoleucine (#p < 0.0001). Data represent the mean ± SEM. Source data are provided as a Source Data file.