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Hu, C.* ; Hoene, M.* ; Plomgaard, P.* ; Hansen, J.S.* ; Zhao, X.* ; Li, J.* ; Wang, X.* ; Clemmesen, J.O.* ; Secher, N.H.* ; Häring, H.-U. ; Lehmann, R. ; Xu, G.* ; Weigert, C.

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

J. Clin. Endocrinol. Metab. 105, 1196–1209 (2020)
Verlagsversion Postprint DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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 O-2 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 hepatosplanchnic 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Capillary Electrophoresis ; Metabolomics ; Succinate ; Exercise ; Liver ; Camp; Fatty-acid-composition; Splanchnic Regulation; Adipose-tissue; Medium-chain; Succinate; Blood; Biomarker; Inhibition; Mechanism; Fumarate
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Zeitschrift Journal of Clinical Endocrinology & Metabolism, The
Quellenangaben Band: 105, Heft: 4, Seiten: 1196–1209 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research and Metabolic Diseases (IDM)