Phosphoinositide dependent protein kinase 1 is required for exercise-induced cardiac hypertrophy but not the associated mitochondrial adaptations.

Academic Article

Abstract

  • Phosphoinositide-dependent protein kinase-1 (PDPK1) is an important mediator of phosphatidylinositol 3-kinase (PI3K) signaling. We previously reported that PI3K but not Akt signaling mediates the increase in mitochondrial oxidative capacity following physiological cardiac hypertrophy. To determine if PDPK1 regulates these metabolic adaptations we examined mice with cardiomyocyte-specific heterozygous knockout of PDPK1 (cPDPK1(+/-)) after 5 wk. exercise swim training. Akt phosphorylation at Thr308 increased by 43% in wildtype (WT) mice but not in cPDPK1(+/-) mice following exercise training. Ventricular contractile function was not different between WT and cPDPK1(+/-) mice at baseline. In addition, exercise did not influence ventricular function in WT or cPDPK1(+/-) mice. Heart weight normalized to tibia length ratios increased by 13.8% in WT mice (6.2±0.2 vs. 7.1±0.2, P=0.001), but not in cPDPK1(+/-) (6.2±0.3 vs. 6.5±0.2, P=0.20) mice after swim training. Diastolic LV dimension increased in WT mice (3.7±0.1 vs. 4.0±0.1 mm, P=0.01) but not in cPDPK1(+/-) (3.8±0.1 vs. 3.7±0.1 mm, P=0.56) following swim training. Maximal mitochondrial oxygen consumption (VADP, nmol/min/mg) using palmitoyl carnitine as a substrate was significantly increased in mice of all genotypes following swim training (WT: 13.6±0.6 vs.16.1±0.9, P=0.04; cPDPK1(+/-): 12.4±0.6 vs.15.9±1.2, P=0.04). These findings suggest that PDPK1 is required for exercise-induced cardiac hypertrophy but does not contribute to exercise-induced increases in mitochondrial function.
  • Authors

    Keywords

  • Cardiac hypertrophy, Exercise, Mitochondria, PI3 kinase signaling, 3-Phosphoinositide-Dependent Protein Kinases, Adaptation, Physiological, Animals, Cardiac Catheterization, Cardiomegaly, Gene Deletion, Heart Failure, Homozygote, Insulin, Mice, Inbred C57BL, Mice, Knockout, Mitochondria, Heart, Models, Biological, Myocytes, Cardiac, Organ Size, Phosphorylation, Phosphothreonine, Physical Conditioning, Animal, Proto-Oncogene Proteins c-akt, Signal Transduction, Ultrasonography, Ventricular Function, Left
  • Digital Object Identifier (doi)

    Author List

  • Noh J; Wende AR; Olsen CD; Kim B; Bevins J; Zhu Y; Zhang Q-J; Riehle C; Abel ED
  • Start Page

  • 297
  • End Page

  • 305
  • Volume

  • 89
  • Issue

  • Pt B