Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise. / Hingst, Janne Rasmuss; Kjøbsted, Rasmus; Birk, Jesper Bratz; Jørgensen, Nicolas Oldenburg; Larsen, Magnus R; Kido, Kohei; Larsen, Jeppe Kjærgaard; Kjeldsen, Sasha Alexandra Sampson; Fentz, Joachim; Frøsig, Christian; Holm, Stephanie; Fritzen, Andreas Mæchel; Dohlmann, Tine Lovsø; Larsen, Steen; Foretz, Marc; Viollet, Benoit; Schjerling, Peter; Overby, Peter; Halling, Jens Frey; Pilegaard, Henriette; Hellsten, Ylva; Wojtaszewski, Jørgen.

I: Molecular Metabolism, Bind 40, 101028, 2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Hingst, JR, Kjøbsted, R, Birk, JB, Jørgensen, NO, Larsen, MR, Kido, K, Larsen, JK, Kjeldsen, SAS, Fentz, J, Frøsig, C, Holm, S, Fritzen, AM, Dohlmann, TL, Larsen, S, Foretz, M, Viollet, B, Schjerling, P, Overby, P, Halling, JF, Pilegaard, H, Hellsten, Y & Wojtaszewski, J 2020, 'Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise', Molecular Metabolism, bind 40, 101028. https://doi.org/10.1016/j.molmet.2020.101028

APA

Hingst, J. R., Kjøbsted, R., Birk, J. B., Jørgensen, N. O., Larsen, M. R., Kido, K., ... Wojtaszewski, J. (2020). Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise. Molecular Metabolism, 40, [101028]. https://doi.org/10.1016/j.molmet.2020.101028

Vancouver

Hingst JR, Kjøbsted R, Birk JB, Jørgensen NO, Larsen MR, Kido K o.a. Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise. Molecular Metabolism. 2020;40. 101028. https://doi.org/10.1016/j.molmet.2020.101028

Author

Hingst, Janne Rasmuss ; Kjøbsted, Rasmus ; Birk, Jesper Bratz ; Jørgensen, Nicolas Oldenburg ; Larsen, Magnus R ; Kido, Kohei ; Larsen, Jeppe Kjærgaard ; Kjeldsen, Sasha Alexandra Sampson ; Fentz, Joachim ; Frøsig, Christian ; Holm, Stephanie ; Fritzen, Andreas Mæchel ; Dohlmann, Tine Lovsø ; Larsen, Steen ; Foretz, Marc ; Viollet, Benoit ; Schjerling, Peter ; Overby, Peter ; Halling, Jens Frey ; Pilegaard, Henriette ; Hellsten, Ylva ; Wojtaszewski, Jørgen. / Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise. I: Molecular Metabolism. 2020 ; Bind 40.

Bibtex

@article{be35a7f42450416280dbf6e514d499e5,
title = "Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise",
abstract = "Objective: Current evidence for AMPK-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption of AMPK function. Findings based on such models are potentially biased by secondary effects related to chronic lack of AMPK function. In an attempt to study the direct effect(s) of AMPK on muscle metabolism during exercise, we generated a new mouse model with inducible muscle-specific deletion of AMPKα catalytic subunits in adult mice.Methods: Tamoxifen-inducible and muscle-specific AMPKα1/α2 double KO mice (AMPKα imdKO) were generated using the Cre/loxP system with the Cre driven by the human skeletal muscle actin (HSA) promotor.Results: During treadmill running at the same relative exercise intensity, AMPKα imdKO mice showed greater depletion of muscle ATP, which was associated with accumulation of the deamination product IMP. Muscle-specific deletion of AMPKα in adult mice promptly reduced maximal running speed, muscle glycogen content and was associated with reduced expression of UGP2, a key component of the glycogen synthesis pathway. Muscle mitochondrial respiration, whole body substrate utilization as well as muscle glucose uptake and fatty acid (FA) oxidation during muscle contractile activity remained unaffected by muscle-specific deletion AMPKα subunits in adult mice.Conclusions: Inducible deletion of AMPKα subunits in adult mice reveals that AMPK is required for maintaining muscle ATP levels and nucleotide balance during exercise, but is dispensable for regulating muscle glucose uptake, FA oxidation and substrate utilization during exercise.",
keywords = "Faculty of Science, AMPK, Exercise, Glucose uptake, Muscle metabolism, Fat oxidation, Glycogen",
author = "Hingst, {Janne Rasmuss} and Rasmus Kj{\o}bsted and Birk, {Jesper Bratz} and J{\o}rgensen, {Nicolas Oldenburg} and Larsen, {Magnus R} and Kohei Kido and Larsen, {Jeppe Kj{\ae}rgaard} and Kjeldsen, {Sasha Alexandra Sampson} and Joachim Fentz and Christian Fr{\o}sig and Stephanie Holm and Fritzen, {Andreas M{\ae}chel} and Dohlmann, {Tine Lovs{\o}} and Steen Larsen and Marc Foretz and Benoit Viollet and Peter Schjerling and Peter Overby and Halling, {Jens Frey} and Henriette Pilegaard and Ylva Hellsten and J{\o}rgen Wojtaszewski",
note = "Copyright {\circledC} 2020. Published by Elsevier GmbH.",
year = "2020",
doi = "10.1016/j.molmet.2020.101028",
language = "English",
volume = "40",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Inducible deletion of skeletal muscle AMPKℵ 1 reveals that AMPK is required for nucleotide balance but 2 dispensable for muscle glucose uptake and fat oxidation during exercise

AU - Hingst, Janne Rasmuss

AU - Kjøbsted, Rasmus

AU - Birk, Jesper Bratz

AU - Jørgensen, Nicolas Oldenburg

AU - Larsen, Magnus R

AU - Kido, Kohei

AU - Larsen, Jeppe Kjærgaard

AU - Kjeldsen, Sasha Alexandra Sampson

AU - Fentz, Joachim

AU - Frøsig, Christian

AU - Holm, Stephanie

AU - Fritzen, Andreas Mæchel

AU - Dohlmann, Tine Lovsø

AU - Larsen, Steen

AU - Foretz, Marc

AU - Viollet, Benoit

AU - Schjerling, Peter

AU - Overby, Peter

AU - Halling, Jens Frey

AU - Pilegaard, Henriette

AU - Hellsten, Ylva

AU - Wojtaszewski, Jørgen

N1 - Copyright © 2020. Published by Elsevier GmbH.

PY - 2020

Y1 - 2020

N2 - Objective: Current evidence for AMPK-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption of AMPK function. Findings based on such models are potentially biased by secondary effects related to chronic lack of AMPK function. In an attempt to study the direct effect(s) of AMPK on muscle metabolism during exercise, we generated a new mouse model with inducible muscle-specific deletion of AMPKα catalytic subunits in adult mice.Methods: Tamoxifen-inducible and muscle-specific AMPKα1/α2 double KO mice (AMPKα imdKO) were generated using the Cre/loxP system with the Cre driven by the human skeletal muscle actin (HSA) promotor.Results: During treadmill running at the same relative exercise intensity, AMPKα imdKO mice showed greater depletion of muscle ATP, which was associated with accumulation of the deamination product IMP. Muscle-specific deletion of AMPKα in adult mice promptly reduced maximal running speed, muscle glycogen content and was associated with reduced expression of UGP2, a key component of the glycogen synthesis pathway. Muscle mitochondrial respiration, whole body substrate utilization as well as muscle glucose uptake and fatty acid (FA) oxidation during muscle contractile activity remained unaffected by muscle-specific deletion AMPKα subunits in adult mice.Conclusions: Inducible deletion of AMPKα subunits in adult mice reveals that AMPK is required for maintaining muscle ATP levels and nucleotide balance during exercise, but is dispensable for regulating muscle glucose uptake, FA oxidation and substrate utilization during exercise.

AB - Objective: Current evidence for AMPK-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption of AMPK function. Findings based on such models are potentially biased by secondary effects related to chronic lack of AMPK function. In an attempt to study the direct effect(s) of AMPK on muscle metabolism during exercise, we generated a new mouse model with inducible muscle-specific deletion of AMPKα catalytic subunits in adult mice.Methods: Tamoxifen-inducible and muscle-specific AMPKα1/α2 double KO mice (AMPKα imdKO) were generated using the Cre/loxP system with the Cre driven by the human skeletal muscle actin (HSA) promotor.Results: During treadmill running at the same relative exercise intensity, AMPKα imdKO mice showed greater depletion of muscle ATP, which was associated with accumulation of the deamination product IMP. Muscle-specific deletion of AMPKα in adult mice promptly reduced maximal running speed, muscle glycogen content and was associated with reduced expression of UGP2, a key component of the glycogen synthesis pathway. Muscle mitochondrial respiration, whole body substrate utilization as well as muscle glucose uptake and fatty acid (FA) oxidation during muscle contractile activity remained unaffected by muscle-specific deletion AMPKα subunits in adult mice.Conclusions: Inducible deletion of AMPKα subunits in adult mice reveals that AMPK is required for maintaining muscle ATP levels and nucleotide balance during exercise, but is dispensable for regulating muscle glucose uptake, FA oxidation and substrate utilization during exercise.

KW - Faculty of Science

KW - AMPK

KW - Exercise

KW - Glucose uptake

KW - Muscle metabolism

KW - Fat oxidation

KW - Glycogen

U2 - 10.1016/j.molmet.2020.101028

DO - 10.1016/j.molmet.2020.101028

M3 - Journal article

C2 - 32504885

VL - 40

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

M1 - 101028

ER -

ID: 242614224