Figure 6.
Amino acid supplementation protects from denervation-induced atrophy without promoting muscle fiber shift
(A) The most significantly altered metabolites resulting from metabolomic analysis of GC muscles are shown in the table. The denervated/innervated ratio is represented in euthyroid and hyperthyroid GC muscles. The denervated/innervated ratio of α-KG, citrate, and glucose levels in euthyroid and hyperthyroid conditions are shown below.
(B and C) Timeline of α-KG (left) and Gln (right) supplementation in denervation experiments. H&E staining of innervated CTR and denervated TA muscles from α-KG- (B) and Gln (C)-supplemented mice. Scale bar, 50 μm. The graphical representation of CSA of TA muscle fibers is shown below each H&E panel.
(D and E) mRNA expression levels of neoMHC and the ratio MHC class II/MHC class I were measured in innervated CTR and denervated GC muscles. Each graph shows TH-treated (left, gray box), α-KG-supplemented (middle), and Gln-supplemented (right) GC muscles. Levels of indicated genes are relative to Cyclophilin-A mRNA used as an internal CTR and normalized to the CTR muscle.
(F) Mitochondrial activity was measured by FACS using MitoTracker Red CMXRos dye in innervated CTR and denervated GC muscles as in (D) and (E). The bar graph shows the relative median fluorescence versus CTR muscles arbitrarily set at 100. Data represent the mean ± SD of the mean of nine replicates. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001.
