Acute endurance exercise increases the nuclear abundance of PGC-1 in trained human skeletal muscle

Little JP, Safdar A, Cermak N, Tarnopolsky MA, Gibala MJ. Acute endurance exercise increases the nuclear abundance of PGC-1 in trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 298: R912–R917, 2010. First published January 27, 2010; doi:10.1152/ajpregu.00409.2009.—Peroxisome proliferator-activated receptor gamma coactivator (PGC-1 ) is a transcriptional coactivator that plays a key role in coordinating mitochondrial biogenesis. Recent evidence has linked p38 MAPK and AMPK with activation of PGC-1 . It was recently shown in rodent skeletal muscle that acute endurance exercise causes a shift in the subcellular localization of PGC-1 from the cytosol to the nucleus, allowing PGC-1 to coactivate transcription factors and increase mitochondrial gene expression, but human data are limited and equivocal in this regard. Our purpose was to examine p38 MAPK and AMPK activation, and PGC-1 protein content in whole muscle, cytosolic, and nuclear fractions of human skeletal muscle following an acute bout of endurance exercise. Eight trained men (29 3 yr; V̇O2peak 55 2 ml·kg ·min ) cycled for 90 min at 65% of V̇O2peak and needle biopsy samples (vastus lateralis) were obtained before and immediately after exercise. At rest, the majority of PGC-1 was detected in cytosolic compared with the nuclear fractions. In response to exercise, nuclear PGC-1 protein increased by 54% (P 0.05), yet whole muscle PGC-1 protein was unchanged compared with rest. Whole muscle and cytosolic p38 MAPK phosphorylation increased severalfold immediately after exercise compared with rest (P 0.05). Acetyl CoA carboxylase (ACC) phosphorylation, a marker of AMPK activation, was increased by 5-fold in cytosolic fractions following exercise (P 0.05). These data provide evidence that, in human skeletal muscle, activation of cytosolic p38 MAPK and AMPK may be potential signals that lead to increased nuclear abundance and activation of PGC-1 in response to an acute bout of endurance exercise.