Niels Jessen

AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

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  • Joachim Fentz, Københavns Universitet
  • ,
  • Rasmus Kjøbsted, Københavns Universitet, Danmark
  • Jesper B. Birk, Københavns Universitet, Danmark
  • Andreas B. Jordy, Københavns Universitet
  • ,
  • Jacob Jeppesen, Københavns Universitet
  • ,
  • Kasper Thorsen
  • Peter Schjerling, Københavns Universitet
  • ,
  • Bente Kiens, Københavns Universitet
  • ,
  • Niels Jessen
  • Benoit Viollet, Université Descartes, Sorbonne Paris Cité, Danmark
  • Jørgen F P Wojtaszewski, Københavns Universitet

The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat diet, or with prolonged fasting. However, in vivo treadmill exercise at the same relative intensity induced a higher RER in AMPKα mdKO mice compared to wild-type (WT = 0.81 6 0.01 (sem); mdKO = 0.87 6 0.02 (sem); P<0.01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKa mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36) and FABPpm (plasma membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA transport capacity and FA transport protein translocation to sarcolemma, respectively. AMPKα is thus required for normal FA metabolism during exercise and muscle contraction.

TidsskriftF A S E B Journal
Sider (fra-til)1725-1738
Antal sider14
StatusUdgivet - 1 maj 2015

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