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 - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Molecular metabolism Année : 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

Marc Foretz
Benoit Viollet

Résumé

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.
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inserm-02870200 , version 1 (16-06-2020)

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Janne Hingst, Rasmus Kjøbsted, Jesper Birk, Nicolas O Jørgensen, Magnus R Larsen, et al.. 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, pp.101028. ⟨10.1016/j.molmet.2020.101028⟩. ⟨inserm-02870200⟩
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