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Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver

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Abstract

As the demand for hepatic glucose production increases during exercise, regulation of liver substrate choice and gluconeogenic activity becomes essential. The aim of the present study was to investigate the effect of a single exercise bout on gluconeogenic protein content and regulation of enzymes involved in substrate utilization in the liver. Mice were subjected to 1 h of treadmill exercise, and livers were removed immediately, 4 or 10 h after exercise. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) mRNA contents in the liver increased immediately after exercise, while the PEPCK protein content increased at 10 h of recovery. Furthermore, 5′AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and pyruvate dehydrogenase (PDH)-E1α Ser293 phosphorylations decreased immediately after exercise. In addition, PDH kinase 4 (PDK4) mRNA and protein content increased immediately after exercise and at 10 h of recovery, respectively. These findings suggest that acute changes in PEPCK and G6Pase protein contents do not contribute to the regulation of gluconeogenic enzyme activity during 1 h of non-exhaustive exercise. In addition, the observation that PDH-E1α, AMPK, and ACC phosphorylation decreased immediately after exercise may indicate that carbohydrates rather than fatty acids are utilized for oxidation in the liver during non-exhaustive exercise.

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Acknowledgments

The study was supported by grants from the Novo Nordisk Foundation, the Lundbeck Foundation, The Danish Research Foundation, The Danish Council for Independent Research in the Natural Sciences, and the Augustinus Foundation.

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The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Centre of Inflammation and Metabolism, The August Krogh Centre, Department of Biology, University of Copenhagen, Universitetsparken 13 4th floor, 2100, Copenhagen, Denmark

    Jakob G. Knudsen, Rasmus S. Biensø, Helle A. Hassing, Anne H. Jakobsen & Henriette Pilegaard

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  1. Jakob G. Knudsen
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  2. Rasmus S. Biensø
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  3. Helle A. Hassing
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  4. Anne H. Jakobsen
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  5. Henriette Pilegaard
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Correspondence to Henriette Pilegaard.

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Knudsen, J.G., Biensø, R.S., Hassing, H.A. et al. Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver. Mol Cell Biochem 403, 209–217 (2015). https://doi.org/10.1007/s11010-015-2351-0

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  • DOI: https://doi.org/10.1007/s11010-015-2351-0

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