Figure 5

Acute elevation in BHBA levels mediated by both R118 and metformin. Male HFD DIO C57BL/6 mice (21 weeks old, 17 weeks on HFD) were fed using control HFD, HFD formulated with 200 mg/kg R118, or HFD formulated with 5 g/kg metformin (n = 12/group). After five weeks of treatment, liver, skeletal muscle, adipose tissue, and plasma were collected for half of the mice in each group (max compound). For the remaining mice, compound-formulated HFD was replaced with control HFD for 24 hours (washout), followed by similar sample collection. Box plots are shown of BHBA measurements from plasma, liver, skeletal muscle, and adipose tissue from R118-fed, metformin-fed, and control HFD fed animals, both in the presence of drug and after drug washout. Data are scaled such that the median value measured across all samples was set to 1.0. * represents p < 0.05; # represents 0.05 < p < 0.1.