Fig. 7: Mechanistic hypothesis: AMPK activity modulates exercise-induced reductions in metabolic efficiency and organ structural changes.

A Schematic representation of mouse exercise training model and downstream analyses performed. B Example of kidneys volume quantification using a 7-Tesla MRI scans and home-based MATLAB postprocessing image analysis. C Volume of total kidney in control and exercise mice. D Left: Representative hematoxylin and eosin staining of control (top) and exercised (bottom) livers, with a ROI showing the boundaries used to count. Right: Blind quantification of nuclei shown as the average number of nuclei across 10 random fields from each organ, n = 12 Control, n = 8 Exercise mice. E Relative mitochondrial DNA expression of S16 and ND1 (mtDNA) normalized to nuclear DNA (mtDNA/nDNA). F Overlap of cytokines known to be released after exercise (termed exerkines) and predicted upstream regulators generated from IPA cytokine analysis of liver proteomics in control and exercise mice. G Volcano plot of predicted upstream regulators generated from IPA transcription factor analysis of liver proteomic in control and exercise mice, with MTOR (downregulated, blue) and YAP1 (upregulated, red) highlighted. Data are means ± SD. *p < 0.05, **P < 0.01, ****p < 0.0001. Statistical analyses were performed using the Signed Rank Wilcoxon test in C and using unpaired Student’s t-test in (D, E). n = 3 per group in (C, E); n = 4 per group in (F, G). Blind quantification of nuclei per region of interest across 4 random fields from each organ sample (n ≥ 2 per group) in (E). cm centimetres, MRI magnetic resonance imaging, mtDNA mitochondrial DNA, nDNA nuclear DNA.