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

TY - JOUR

T1 - AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

AU - Fentz, Joachim

AU - Kjøbsted, Rasmus

AU - Birk, Jesper Bratz

AU - Jordy, Andreas Børsting

AU - Jeppesen, Jacob Fuglsbjerg

AU - Thorsen, Kasper

AU - Schjerling, Peter

AU - Kiens, Bente

AU - Jessen, Niels

AU - Viollet, Benoit

AU - Wojtaszewski, Jørgen

N1 - CURIS 2015 NEXS 058

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

U2 - 10.1096/fj.14-266650

DO - 10.1096/fj.14-266650

M3 - Journal article

C2 - 25609422

SN - 0892-6638

VL - 29

SP - 1725

EP - 1738

JO - F A S E B Journal

JF - F A S E B Journal

IS - 5

ER -