Fig. 1

Regulatory hubs under PGC-1α1 control in skeletal muscle. a Transcriptomics and metabolomics analysis of mck-PGC-1α1 skeletal muscle. b Integrated pathway analysis of mck-PGC-1α1 transcriptomics and metabolomics. c Metabolite enrichment analysis of mck-PGC-1α1. d Relative levels of aspartate and glutamate in skeletal muscle of wt and mck-PGC-1α1 mice (n = 5). e Schematic representation of the role of GOT2 in aspartate synthesis. f Overlapping Kat-associated networks. g Functional annotation of the Kat-associated network. h Relative levels of malate in skeletal muscle of wt and mck-PGC-1α1 mice (n = 5). i Relative levels of glutamate in primary myotubes transduced with Gfp control or Pgc-1α1 adenovirus and supplemented with 1 μM kynurenine (Kyn) (n = 4) j Relative levels of aspartate in primary myotubes transduced with Pgc-1α1 adenovirus treated with 0, 1 or 10 μM Kyn (n = 4). k Schematic representation of how skeletal muscle PGC-1α1 integrates Kyn metabolism with aspartate biosynthesis and the malate-aspartate shuttle. Bars depict mean values and error bars indicate SEM. Unpaired, two-tailed student’s t-test was used when two groups were compared, and one-way analysis of variance (ANOVA) followed by Fisher’s least significance difference (LSD) test for post hoc comparisons were used to compare multiple groups, *p < 0.05