Figure 6

Chronic metformin treatment results in increased plasma levels of purine metabolites. 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 cmp). For the remaining mice, compound-formulated HFD was replaced with control HFD for 24 hours (washout), followed by similar sample collection. Detected changes in plasma purine metabolites for both R118 and metformin-treated mice are shown relative to control HFD in heatmap format, along with a schematic illustrating the purine catabolism pathway. Intermediates highlighted using red boxes are significantly elevated in metformin washout samples.