ArticleThe Journal of clinical endocrinology and metabolism2020
Muscle-Liver Substrate Fluxes in Exercising Humans and Potential Effects on Hepatic Metabolism.
Article in The Journal of clinical endocrinology and metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- The Ergogenic Potential of Succinic Acid in Exercise Performance and Post-Exercise Recovery: A Systematic Review.Nutrients · 2026Pooled it
- Exercise increases TCA intermediate concentrations during low-calorie diet independent of insulin resistance among women with obesity.Physiological reports · 2024Trial
- Succinate and lactate produced as conserved biomarkers through chronic and transient substrate-level phosphorylation: from microorganisms to cancer.Journal of bioenergetics and biomembranes · 2026Review
- The effects of 10 months of exercise on circulating ketone body concentration among children.Pediatric research · 2026Article
- What Do We Know of Human Fuel Use during Aerobic Exercise, and How Do We Know It?Physiology (Bethesda, Md.) · 2026Review
- Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation.Journal of translational medicine · 2025Review
- Liver as a nexus of daily metabolic cross talk.International review of cell and molecular biology · 2025Review
- The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.The Journal of endocrinology · 2024Review
- Article
- Chronic exercise improves hepatic acylcarnitine handling.iScience · 2024Article
- Metabolic consequences of skeletal muscle- and liver-specific BBSome deficiency.American journal of physiology. Endocrinology and metabolism · 2023Article
- Chrono-exercise: Time-of-day-dependent physiological responses to exercise.Sports medicine and health science · 2023Review
- Black Ginger (Nutrients · 2022Article
- Metabolic flux between organs measured by arteriovenous metabolite gradients.Experimental & molecular medicine · 2022Review
- Effect of acute swimming exercise at different intensities but equal total load over metabolic and molecular responses in swimming rats.Journal of muscle research and cell motility · 2022Article
- Effects of Endurance Training on the Coenzyme Q Redox State in Rat Heart, Liver, and Brain at the Tissue and Mitochondrial Levels: Implications for Reactive Oxygen Species Formation and Respiratory Chain Remodeling.International journal of molecular sciences · 2022Article
- The pathophysiology of motor fatigue and fatigability in multiple sclerosis.Frontiers in neurology · 2022Review
- Cutting edge concepts: Does bilirubin enhance exercise performance?Frontiers in sports and active living · 2022Review
- Nitrate exposure reprograms hepatic amino acid and nutrient sensing pathways prior to exercise: A metabolomic and transcriptomic investigation in zebrafishFrontiers in molecular biosciences · 2022Article
- Exercise prevents fatty liver by modifying the compensatory response of mitochondrial metabolism to excess substrate availability.Molecular metabolism · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
contextThe liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism.
objectiveWe aim to elucidate which metabolites are released from the working muscles and taken up by the liver in exercising humans and their potential influence on hepatic function.
methodsIn two separate studies, young healthy men fasted overnight and then performed an acute bout of exercise. Arterial-to-venous differences of metabolites over the hepato-splanchnic bed and over the exercising and resting leg were investigated by capillary electrophoresis- and liquid chromatography-mass spectrometry metabolomics platforms. Liver transcriptome data of exercising mice were analyzed by pathway analysis to find a potential overlap between exercise-regulated metabolites and activators of hepatic transcription.
resultsDuring exercise, hepatic O2 uptake and CO2 delivery were increased two-fold. In contrast to all other free fatty acids (FFA), those FFA with 18 or more carbon atoms and a high degree of saturation showed a constant release in the liver vein and only minor changes by exercise. FFA 6:0 and 8:0 were released from the working leg and taken up by the hepato-splanchnic bed. Succinate and malate showed a pronounced hepatic uptake during exercise and were also released from the exercising leg. The transcriptional response in the liver of exercising mice indicates the activation of HIF-, NRF2-, and cAMP-dependent gene transcription. These pathways can also be activated by succinate.
conclusionMetabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.
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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.