ArticleHuman molecular genetics2019
Dystrophinopathy-associated dysfunction of Krebs cycle metabolism.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Viscoelastic properties of dystrophin-deficient mouse skeletal muscles are resilient to isometric fatiguing exercise.Physiological reports · 2026Article
- Immunoproteasome Inhibition Positively Impacts the Gut-Muscle Axis in Duchenne Muscular Dystrophy.Journal of cachexia, sarcopenia and muscle · 2025Article
- Stress exposure in the mdx mouse model of Duchenne muscular dystrophy provokes a widespread metabolic response.The FEBS journal · 2025Article
- Transcriptomic profiling of skeletal muscle in the DMDScientific reports · 2025Article
- The Gut Microbiota Involvement in the Panorama of Muscular Dystrophy Pathogenesis.International journal of molecular sciences · 2024Review
- Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients' Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2023Review
- "suMus," a novel digital system for arm movement metrics and muscle energy expenditure.Frontiers in physiology · 2023Article
- Article
- The Effect of Uridine on the State of Skeletal Muscles and the Functioning of Mitochondria in Duchenne Dystrophy.International journal of molecular sciences · 2022Article
- Bioenergetic and Metabolic Impairments in Induced Pluripotent Stem Cell-Derived Cardiomyocytes Generated from Duchenne Muscular Dystrophy Patients.International journal of molecular sciences · 2022Article
- Article
- Biomarkers in Duchenne Muscular Dystrophy.Current heart failure reports · 2022Review
- Complexity of skeletal muscle degeneration: multi-systems pathophysiology and organ crosstalk in dystrophinopathy.Pflugers Archiv : European journal of physiology · 2021Review
- Muscle metabolic remodelling patterns in Duchenne muscular dystrophy revealed by ultra-high-resolution mass spectrometry imaging.Scientific reports · 2021Article
- Multiomics analysis of the mdx/mTR mouse model of Duchenne muscular dystrophy.Connective tissue research · 2021Article
- Complementary NADSkeletal muscle · 2020Article
- Longitudinal metabolomic analysis of plasma enables modeling disease progression in Duchenne muscular dystrophy mouse models.Human molecular genetics · 2020Article
- Metabolic reprogramming of fibro/adipogenic progenitors facilitates muscle regeneration.Life science alliance · 2020Article
- Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
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 urine. Five of seven detected Krebs cycle metabolites were depleted in mdx urine, with succinate being the most robustly affected metabolite. Using selected reaction monitoring mass spectrometry, we demonstrated that muscle-specific dystrophin expression corrects mdx succinate depletion. When subjected to downhill treadmill running, wild-type and mdx mice expressing recombinant dystrophin in skeletal muscle displayed significant increases in urinary succinate levels. However, mdx succinate levels were unchanged, suggesting urinary succinate depletion may reflect an inability to upregulate the Krebs cycle following exercise. Finally, we show that supplementing the Krebs cycle in an ex vivo fatigue/recovery assay significantly impacts mdx muscle performance but has no effect on wild-type muscle. Our results suggest that global metabolic impairment is associated with mdx disease progression and that Krebs cycle deficiencies are a downstream consequence of dystrophin loss.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.