Fig 3. Comparison of pharmacological AMPK activation and exercise in lean C57BL/6 mice (n = 8).

Effects of pharmacological AMPK activation on fasting blood glucose (FBG) and pACC/ACC ratio 1h (A) and 5h (B) post dose (LA2, 3 and 30 mg/kg, PO and SA2, 3 and 20 mg/kg, PO) in 12-week old lean C57BL/6 mice. The effects of 130 min treadmill exercise on pACC/ACC ratio (treadmill exercise at speed of 10 m/min) are also shown in (B); Data are represented as mean ± SEM. *p < 0.05, **p < 0. 01, ***p < 0.001 relative to vehicle. (C) Acute exercise and pharmacological AMPK activation have robust transcriptional effects in heart, skeletal muscle, and liver (n = 5). Tissues were collected 5 h post dose, or at the end of exercise. Shown are the number of probesets (y-axis) that met the fold change cutoffs (x-axis). Only the probesets with FDR_BH (False Discovery Rate Benjamini & Hochberg) p<0.1 were included. (D) For skeletal muscle gene expression profiling, 789 probesets are shown that met the +/- 1.2 fold change and FDR_BH p<0.1 threshold in both the exercise and LA2 (30 mg/kg, PO) groups (indicated by grey dots). The color gradient represents fold change compared to vehicle treated sedentary mice (-2.0 to 2.0 fold). (E) Pathway analysis of heart, skeletal muscle, liver, BAT, and WAT of C57BL/6 mice (1) exercised on treadmill for 130 min; and (2) treated with LA2 (30 mg/kg, PO). White boxes represent changes that did not reach statistical significance (1.2 fold and p<0.05). (F) Fkbp5 was one of six genes (represented by 7 probesets) that were significantly regulated by both acute exercise and acute pharmacological AMPK activation (LA2, 30 mg/kg, PO) in all 5 tissues profiled. Shown in the box plot are the log2_Intensity values per treatment group. (G) Schematic diagram summarizing the pathways regulated by exercise and direct AMPK activation.