biostudies-literatureLindsay AArkansas Humanities CouncilUniversity of MinnesotaNational Institutes of HealthNIAMS NIH HHSMuscular Dystrophy Association942-951https://www.ebi.ac.uk/biostudies/studies/S-EPMC6400043biostudies-literatureUnknown28(6)Duchenne muscular dystrophy is a deadly muscle-wasting disorder caused by loss of dystrophin protein. Studies suggest that metabolic alterations are important to disease pathogenesis. Because muscle accounts for ~40% of body mass, we hypothesized that dystrophy-mediated metabolic changes would be measurable in biofluids and that a metabolomic analysis of urine would provide insight into the metabolic status of dystrophic muscle. Using the mdx mouse model, we performed a large-scale metabolomic screen at 1 and 3 months. While 10% of metabolites were altered at age 1 month, 40% were changed at 3 months. Principal component analysis distinguished wild-type from mdx animals, with the greatest separation at 3 months. A critical distinguishing pathway was Krebs cycle metabolite depletion in mdx Human molecular geneticsDystrophinopathy-associated dysfunction of Krebs cycle metabolism.PMC6400043R01 AR049899RO1 AR049899R01 AR042423RO1 AR042423349549Lowe DAWitthuhn BAChamberlain CMLindsay AErvasti JMfalseDystrophinopathy-associated dysfunction of Krebs cycle metabolism.Duchenne muscular dystrophy is a deadly muscle-wasting disorder caused by loss of dystrophin protein. Studies suggest that metabolic alterations are important to disease pathogenesis. Because muscle accounts for ~40% of body mass, we hypothesized that dystrophy-mediated metabolic changes would be measurable in biofluids and that a metabolomic analysis of urine would provide insight into the metabolic status of dystrophic muscle. Using the mdx mouse model, we performed a large-scale metabolomic screen at 1 and 3 months. While 10% of metabolites were altered at age 1 month, 40% were changed at 3 months. Principal component analysis distinguished wild-type from mdx animals, with the greatest separation at 3 months. A critical distinguishing pathway was Krebs cycle metabolite depletion in mdx 2019-01-01T00:00:00Z2019 Mar2025-04-22T03:01:18.02Z2020-05-22T12:20:54ZS-EPMC64000433047617110.1093/hmg/ddy404