Fig. 2
Effect of loss of FGF21 on critical illness-induced muscle wasting and weakness. a EDL muscle absolute maximal tetanic force. 2-way-ANOVA interaction p = 0.03. b EDL muscle specific maximal tetanic force. c Tibialis muscle wet weight. At 5 days, 2-way-ANOVA p = 0.6. d Tibialis muscle dry weight. e EDL muscle wet weight. 2-way-ANOVA p = 0.5. f EDL muscle dry weight. 2-way-ANOVA p = 0.5. g Muscle atrophy markers. Relative mRNA expression of F-box protein 32 (also known as Atrogin-1) (Fbxo32) and Tripartite motif containing 63 (also known as Muscle-ring-finger-1) (Trim63) in gastrocnemius muscle. h Ratio of phosphorylated over total p70S6 kinase (p70S6K1) and Eukaryotic translation initiation factor 2α (eIF2α) protein expression in gastrocnemius muscle. i Markers of mitochondrial function. Muscle citrate synthase and respiratory chain complex I and V activity in tibialis anterior muscle. Complex V 2-way-ANOVA p = 0.2. j Autophagy markers. Relative protein expression of Microtubule-associated protein light chain-3, mature-form (LC3-II) and p62 and relative mRNA expression of p62 in gastrocnemius muscle. k Relative mRNA expression of ER stress response markers, Spliced X-box binding protein 1 (Xbp1s), Heat shock protein family A member 5 (Hspa5), Activating transcription factor 4 (Atf4), DNA damage inducible transcript 3 (Ddit3), Calreticulin (Calr), Protein disulphide isomerase family A member 4 (Pdia4) in gastrocnemius muscle. Gene and protein expression are shown relative to the mean of healthy Fgf21+/+ mice. a, b, e, f Healthy control, Fgf21+/+: n = 15; Healthy control, Fgf21−/−: n = 16; Critically ill, Fgf21+/+: n = 14; Critically ill Fgf21−/−: n = 16. c, d, g, h Healthy control, Fgf21+/+: n = 15 at 30 h, n = 21 at 5 days; Healthy control, Fgf21−/−: n = 15 at 30 h, n = 24 at 5 days; Critically ill, Fgf21+/+: n = 15 at 30 h, n = 19 at 5 days; Critically ill, Fgf21−/−: n = 15 at 30 h, n = 18 at 5 days. i-k Healthy control, Fgf21+/+: n = 21; Healthy control, Fgf21−/−: n = 24; Critically ill, Fgf21+/+: n = 19; Critically ill, Fgf21−/−: n = 18. * p < 0.05, ** p < 0.01, *** p < 0.001 between healthy control and critically ill mice and § p < 0.05, §§ p < 0.01 and §§§ p < 0.001 between Fgf21+/+ and Fgf21−/− mice