Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area

Kathleen Sturgeon, Geetha Muthukumaran, Dennis Ding, Akinyemi Bajulaiye, Victor Ferrari, Joseph R. Libonati

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The aim of this study was to examine the impact of moderate-intensity treadmill exercise on the structure and function of the murine heart and its associated impact on Akt-AMPK-mTOR signaling. A secondary aim was to test whether the exercise phenotype was altered following a cardiotoxic bolus dose of doxorubicin (DOX). Two-month-old C57Bl/6J female mice remained sedentary (SED, n = 12) or were progressively trained with treadmill running for 2 months up to 18 m/min; 60 min/day, 5 days/weeks (EX, n = 11) or EX + DOX (15 mg/kg/dose) (EX + DOX, n = 6). Following treadmill training, mice underwent graded exercise tolerance testing and echocardiography. Training improved graded exercise tolerance by 68 ± 5% relative to SED, and this effect was not altered with bolus DOX. There were no changes in relative heart size with EX or EX + DOX versus SED. Regional posterior wall thickening was improved in EX and abrogated in EX + DOX. EX had a reduced cardiomyocyte cross-sectional area (CSA) relative to SED, and CSA was further attenuated with DOX. Following EX, AMPK-associated phosphorylation of ULK1(ser317) tended to be lower relative to SED. Akt-associated phosphorylation of TSC2(thr1462) and mTOR(ser2448) were also decreased relative to SED. We observed an increase in AMPK activity with DOX that was not translated to downstream AMPK phosphorylation sites. We conclude that 2 months of moderate treadmill exercise training improves regional cardiac function and exercise capacity, but does not induce relative physiologic hypertrophy in female mice. Differential responses in Akt-AMPK-mTOR signaling may mediate the observed phenotype.

Original languageEnglish (US)
Article numbere12406
JournalPhysiological reports
Volume3
Issue number5
DOIs
StatePublished - Jan 1 2015

Fingerprint

Cardiac Myocytes
Doxorubicin
AMP-Activated Protein Kinases
Exercise
Exercise Tolerance
Phosphorylation
Phenotype
Exercise Test
Running
Hypertrophy
Echocardiography

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Sturgeon, Kathleen ; Muthukumaran, Geetha ; Ding, Dennis ; Bajulaiye, Akinyemi ; Ferrari, Victor ; Libonati, Joseph R. / Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area. In: Physiological reports. 2015 ; Vol. 3, No. 5.
@article{6d76ec6938a5475f88729d16f0403708,
title = "Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area",
abstract = "The aim of this study was to examine the impact of moderate-intensity treadmill exercise on the structure and function of the murine heart and its associated impact on Akt-AMPK-mTOR signaling. A secondary aim was to test whether the exercise phenotype was altered following a cardiotoxic bolus dose of doxorubicin (DOX). Two-month-old C57Bl/6J female mice remained sedentary (SED, n = 12) or were progressively trained with treadmill running for 2 months up to 18 m/min; 60 min/day, 5 days/weeks (EX, n = 11) or EX + DOX (15 mg/kg/dose) (EX + DOX, n = 6). Following treadmill training, mice underwent graded exercise tolerance testing and echocardiography. Training improved graded exercise tolerance by 68 ± 5{\%} relative to SED, and this effect was not altered with bolus DOX. There were no changes in relative heart size with EX or EX + DOX versus SED. Regional posterior wall thickening was improved in EX and abrogated in EX + DOX. EX had a reduced cardiomyocyte cross-sectional area (CSA) relative to SED, and CSA was further attenuated with DOX. Following EX, AMPK-associated phosphorylation of ULK1(ser317) tended to be lower relative to SED. Akt-associated phosphorylation of TSC2(thr1462) and mTOR(ser2448) were also decreased relative to SED. We observed an increase in AMPK activity with DOX that was not translated to downstream AMPK phosphorylation sites. We conclude that 2 months of moderate treadmill exercise training improves regional cardiac function and exercise capacity, but does not induce relative physiologic hypertrophy in female mice. Differential responses in Akt-AMPK-mTOR signaling may mediate the observed phenotype.",
author = "Kathleen Sturgeon and Geetha Muthukumaran and Dennis Ding and Akinyemi Bajulaiye and Victor Ferrari and Libonati, {Joseph R.}",
year = "2015",
month = "1",
day = "1",
doi = "10.14814/phy2.12406",
language = "English (US)",
volume = "3",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area. / Sturgeon, Kathleen; Muthukumaran, Geetha; Ding, Dennis; Bajulaiye, Akinyemi; Ferrari, Victor; Libonati, Joseph R.

In: Physiological reports, Vol. 3, No. 5, e12406, 01.01.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Moderate-intensity treadmill exercise training decreases murine cardiomyocyte cross-sectional area

AU - Sturgeon, Kathleen

AU - Muthukumaran, Geetha

AU - Ding, Dennis

AU - Bajulaiye, Akinyemi

AU - Ferrari, Victor

AU - Libonati, Joseph R.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The aim of this study was to examine the impact of moderate-intensity treadmill exercise on the structure and function of the murine heart and its associated impact on Akt-AMPK-mTOR signaling. A secondary aim was to test whether the exercise phenotype was altered following a cardiotoxic bolus dose of doxorubicin (DOX). Two-month-old C57Bl/6J female mice remained sedentary (SED, n = 12) or were progressively trained with treadmill running for 2 months up to 18 m/min; 60 min/day, 5 days/weeks (EX, n = 11) or EX + DOX (15 mg/kg/dose) (EX + DOX, n = 6). Following treadmill training, mice underwent graded exercise tolerance testing and echocardiography. Training improved graded exercise tolerance by 68 ± 5% relative to SED, and this effect was not altered with bolus DOX. There were no changes in relative heart size with EX or EX + DOX versus SED. Regional posterior wall thickening was improved in EX and abrogated in EX + DOX. EX had a reduced cardiomyocyte cross-sectional area (CSA) relative to SED, and CSA was further attenuated with DOX. Following EX, AMPK-associated phosphorylation of ULK1(ser317) tended to be lower relative to SED. Akt-associated phosphorylation of TSC2(thr1462) and mTOR(ser2448) were also decreased relative to SED. We observed an increase in AMPK activity with DOX that was not translated to downstream AMPK phosphorylation sites. We conclude that 2 months of moderate treadmill exercise training improves regional cardiac function and exercise capacity, but does not induce relative physiologic hypertrophy in female mice. Differential responses in Akt-AMPK-mTOR signaling may mediate the observed phenotype.

AB - The aim of this study was to examine the impact of moderate-intensity treadmill exercise on the structure and function of the murine heart and its associated impact on Akt-AMPK-mTOR signaling. A secondary aim was to test whether the exercise phenotype was altered following a cardiotoxic bolus dose of doxorubicin (DOX). Two-month-old C57Bl/6J female mice remained sedentary (SED, n = 12) or were progressively trained with treadmill running for 2 months up to 18 m/min; 60 min/day, 5 days/weeks (EX, n = 11) or EX + DOX (15 mg/kg/dose) (EX + DOX, n = 6). Following treadmill training, mice underwent graded exercise tolerance testing and echocardiography. Training improved graded exercise tolerance by 68 ± 5% relative to SED, and this effect was not altered with bolus DOX. There were no changes in relative heart size with EX or EX + DOX versus SED. Regional posterior wall thickening was improved in EX and abrogated in EX + DOX. EX had a reduced cardiomyocyte cross-sectional area (CSA) relative to SED, and CSA was further attenuated with DOX. Following EX, AMPK-associated phosphorylation of ULK1(ser317) tended to be lower relative to SED. Akt-associated phosphorylation of TSC2(thr1462) and mTOR(ser2448) were also decreased relative to SED. We observed an increase in AMPK activity with DOX that was not translated to downstream AMPK phosphorylation sites. We conclude that 2 months of moderate treadmill exercise training improves regional cardiac function and exercise capacity, but does not induce relative physiologic hypertrophy in female mice. Differential responses in Akt-AMPK-mTOR signaling may mediate the observed phenotype.

UR - http://www.scopus.com/inward/record.url?scp=84990841904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990841904&partnerID=8YFLogxK

U2 - 10.14814/phy2.12406

DO - 10.14814/phy2.12406

M3 - Article

AN - SCOPUS:84990841904

VL - 3

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 5

M1 - e12406

ER -