Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Muscle-liver substrate fluxes in exercising humans and potential effects on hepatic metabolism

Research output: Contribution to journalJournal articleResearchpeer-review

DOI

  1. Migration, gestational diabetes and adverse pregnancy outcomes: a nationwide study of singleton deliveries in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Academic performance in adolescents born to mothers with gestational diabetes - a national Danish cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Expression of cholecystokinin and its receptors in the intestinal tract of type 2 diabetes patients and healthy controls

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: 2 population cohorts

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Neprilysin inhibition increases glucagon levels in humans and mice with potential effects on amino acid metabolism

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. The regulation of circulating hepatokines by fructose ingestion in humans

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

CONTEXT: The liver is crucial to maintain energy homeostasis during exercise. Skeletal muscle-derived metabolites can contribute to the regulation of hepatic metabolism.

OBJECTIVE: We 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.

METHODS: In 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.

RESULTS: During 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.

CONCLUSION: Metabolites circulate between working muscles and the liver and may support the metabolic adaption to exercise by acting both as substrates and as signaling molecules.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume105
Issue number4
Pages (from-to)1196-1209
Number of pages14
ISSN0021-972X
DOIs
Publication statusPublished - 1 Apr 2020

Bibliographical note

© Endocrine Society 2019.

    Research areas

  • CAMP, Capillary electrophoresis, Exercise, Liver, Metabolomics, Succinate

ID: 59167873