ArticleNature communications2019
Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- A Single Exercise Session Elicits a Transient Kynurenine Metabolic Signature in Health and Disease: A Systematic Review and Meta-Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Pooled it
- Exercise-induced adaptations in the kynurenine pathway: implications for health and disease management.Frontiers in sports and active living · 2025Pooled it
- Transcriptomic meta-analysis of disuse muscle atrophy vs. resistance exercise-induced hypertrophy in young and older humans.Journal of cachexia, sarcopenia and muscle · 2021Pooled it
- Effects of Heat Exposure on Kynurenine Pathway Metabolism-Comparison Between Exertional and Exogenous Heating of the Human Body.Acta physiologica (Oxford, England) · 2025Trial
- Direct Effects of Vitamin D Supplementation on Ultramarathon-Induced Changes in Kynurenine Metabolism.Nutrients · 2022Trial
- Review
- Effects of a Multi-Ingredient MCT-Leucine-Creatine-Based Supplement (TLN-01) on Muscle Mass, Strength, and Plasma Amino Acid Profiles in Older Adults with Sarcopenia: A Randomized Controlled Trial.Life (Basel, Switzerland) · 2026Article
- Molecules of mood: the integrated molecular transducers of exercise's antidepressant effects.Molecular genetics and genomics : MGG · 2026Review
- GPR54 regulates non-small cell lung cancer development via dopa decarboxylase.Signal transduction and targeted therapy · 2026Article
- Exercise-induced effects on atherogenesis and tryptophan catabolism via the kynurenine pathway in an HIV-associated atherosclerosis mouse model.Experimental physiology · 2026Article
- Modulation of the Kynurenine Pathway: A New Approach for Treating Neurodegeneration.Life (Basel, Switzerland) · 2026Review
- Elevating Circulating L-Kynurenine Promotes Frailty in Aging Mice.Journal of cachexia, sarcopenia and muscle · 2026Article
- Modulation of the Kynurenine Pathway in Obese Mexican Navy Women Following a Structured Weight Loss Program: A Pre-Post-Intervention Study.Nutrients · 2026Article
- Organ cross-talk: molecular mechanisms, biological functions, and therapeutic interventions for diseases.Signal transduction and targeted therapy · 2026Review
- The Muscle-Liver Immunometabolic Axis in Liver Transplantation: A Decisive Role in Outcomes and Mechanisms.International journal of biological sciences · 2026Review
- Kynurenine Pathway Metabolites as Mediators of Exercise-Induced Mood Enhancement, Fatigue Resistance, and Neuroprotection.International journal of molecular sciences · 2025Review
- NADNature biomedical engineering · 2025Article
- The role of irisin in exercise-induced muscle and metabolic health: a narrative review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Indole-3-propionic acid enhances glycolytic myofiber formation in piglets through PI3K-mTOR activation and gut microbiota-driven tryptophan metabolic alteration.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- From Microbial Switches to Metabolic Sensors: Rewiring the Gut-Brain Kynurenine Circuit.Biomedicines · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
Abstract
The coactivator PGC-1α1 is activated by exercise training in skeletal muscle and promotes fatigue-resistance. In exercised muscle, PGC-1α1 enhances the expression of kynurenine aminotransferases (Kats), which convert kynurenine into kynurenic acid. This reduces kynurenine-associated neurotoxicity and generates glutamate as a byproduct. Here, we show that PGC-1α1 elevates aspartate and glutamate levels and increases the expression of glycolysis and malate-aspartate shuttle (MAS) genes. These interconnected processes improve energy utilization and transfer fuel-derived electrons to mitochondrial respiration. This PGC-1α1-dependent mechanism allows trained muscle to use kynurenine metabolism to increase the bioenergetic efficiency of glucose oxidation. Kat inhibition with carbidopa impairs aspartate biosynthesis, mitochondrial respiration, and reduces exercise performance and muscle force in mice. Our findings show that PGC-1α1 activates the MAS in skeletal muscle, supported by kynurenine catabolism, as part of the adaptations to endurance exercise. This crosstalk between kynurenine metabolism and the MAS may have important physiological and clinical implications.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.