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Myocardial Glycolytic Rate Regulates Exercise‐Induced Physiologic Cardiac Growth
Author(s) -
Gibb Andrew,
Gilbert Lindsey A,
Brittian Kenneth R,
Jones Steven P,
Bhatnagar Aruni,
Hill Bradford G
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1239.7
Subject(s) - medicine , cardiac function curve , endocrinology , sed , cardiology , heart rate , stroke volume , heart failure , muscle hypertrophy , cardiac output , endurance training , myocyte , glycolysis , ejection fraction , hemodynamics , blood pressure , metabolism
BACKGROUND Regular exercise improves quality of life and decreases all‐cause mortality, in part due to improvements in cardiovascular health. Repetitive exercise enhances cardiac function by promoting cardiomyocyte growth and increasing angiogenesis, and is associated with elevated myocardial glucose and fatty acid utilization. Nevertheless, it is unclear whether changes in myocardial metabolism are causative in cardiac adaptations to exercise. In this study, we tested the hypothesis that exercise‐induced increases in myocardial glycolysis are required for physiological cardiac growth. METHODS Fifteen week‐old, male FVB/NJ transgenic (Tg) mice expressing a cardiac‐specific, dominant‐negative form of phosphofructokinase 2, which decreases myocardial glycolytic rate, and their wild‐type (WT) counterparts were subjected to sedentary (SED) conditions or forced treadmill exercise (EXE) for 30 days. Systemic and cardiac‐specific adaptations to exercise were assessed by measuring exercise capacity and echocardiographic changes in cardiac structure and function; biochemical signatures of adaptation were measured by immunohistochemistry, qPCR and immunoblotting. RESULTS In WT mice, exercise training increased distance run by 42% (p<0.0001) and work performed by 69% (p<0.0001). Exercise promoted cardiac growth (heart‐to‐tibia length: SED, 6.7±0.2 mg/mm vs. EXE, 7.7±0.4 mg/mm; p<0.0001), which was due to myocyte hypertrophy (myocyte cross‐sectional area: SED, 461±43 μm 2 vs. EXE, 564±40 μm 2 ; p<0.01). Exercise capacity was not different between WT and Tg mice; however, unlike WT EXE mice, which showed increased end diastolic volume, stroke volume, and cardiac output after exercise (p<0.05), exercise did not change these indices of cardiac function in Tg mice. Interestingly, the Tg SED and EXE mice displayed a hypertrophic heart, characterized by elevated atrial natriuretic peptide (p<0.01), indicating activation of a fetal gene program. Moreover, unlike WT mice, Tg mice failed to show exercise‐induced activation of Akt, which is necessary for physiological cardiac growth and adpatation, and demonstrated lower expression of the pro‐angiogenic factor, VEGF. CONCLUSIONS Diminished cardiac glycolytic rate prevents cardiac adaptations to exercise and may act as a pivotal regulator of physiological and pathological hypertrophic programs. Support or Funding Information ACKNOWLEDGEMENTS: This work was funded by the NIH (GM103492 and HL122580).