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

Junghyun Noh; Adam R Wende; Curtis D Olsen; Bumjun Kim; Jack Bevins; Yi Zhu; Quan-Jiang Zhang; Christian Riehle; E. Dale Abel

doi:10.1016/j.yjmcc.2015.10.015

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

Journal article

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

Junghyun Noh, Adam R Wende, Curtis D Olsen, Bumjun Kim, Jack Bevins, Yi Zhu, Quan-Jiang Zhang, Christian Riehle and E. Dale Abel

Journal of molecular and cellular cardiology, Vol.89(Pt B), pp.297-305

12/2015

DOI: 10.1016/j.yjmcc.2015.10.015

PMCID: PMC4689617

PMID: 26476238

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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±0.1mm, P=0.01) but not in cPDPK1+/− (3.8±0.1 vs. 3.7±0.1mm, 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. •Exercise induces cardiac hypertrophy and mitochondrial oxidative capacity via PI3K-dependent but Akt-Independent pathways.•PI3K activates PDPK1, but its role in the mitochondrial adaptations to exercise-induced hypertrophy is unknown.•Mice with heterozygous deletion of Pdpk1 in cardiomyocytes (cPDPK1+/−) do not activate Akt or hypertrophy after exercise.•Exercise increases mitochondrial oxidative capacity in cPDPK1+/+ and cPDPK1+/− hearts.•Although exercise increases myocardial PI3K activity, the increase in mitochondrial oxidation occurs independently of PDPK1.

Cardiac hypertrophy

Mitochondria

Exercise

PI3 kinase signaling

Details

Title: Subtitle: Phosphoinositide dependent protein kinase 1 is required for exercise-induced cardiac hypertrophy but not the associated mitochondrial adaptations
Creators: Junghyun Noh - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Adam R Wende - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Curtis D Olsen - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Bumjun Kim - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Jack Bevins - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Yi Zhu - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Quan-Jiang Zhang - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Christian Riehle - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
E. Dale Abel - Program in Molecular Medicine and Division of Endocrinology, Metabolism and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA
Resource Type: Journal article
Publication Details: Journal of molecular and cellular cardiology, Vol.89(Pt B), pp.297-305
DOI: 10.1016/j.yjmcc.2015.10.015
PMID: 26476238
PMCID: PMC4689617
NLM abbreviation: J Mol Cell Cardiol
ISSN: 0022-2828
eISSN: 1095-8584
Publisher: Elsevier Ltd
Language: English
Date published: 12/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025290402771

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