Exercise-induced changes in myocardial glucose utilization during periods of active cardiac growth

Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fat...

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Published in:Journal of molecular and cellular cardiology 2024-05, Vol.191, p.50-62
Main Authors: Fulghum, Kyle L., Collins, Helen E., Lorkiewicz, Pawel K., Cassel, Teresa A., Fan, Teresa W.M., Hill, Bradford G.
Format: Article
Language:eng
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Summary:Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fate of carbon derived from dietary glucose in the heart during acute, active, and established phases of exercise-induced cardiac growth. Male and female FVB/NJ mice were subjected to treadmill running for up to 4 weeks and cardiac growth was assessed by gravimetry. Cardiac metabolic responses to exercise were assessed via in vivo tracing of [13C6]-glucose via mass spectrometry and nuclear magnetic resonance. We found that the half-maximal cardiac growth response was achieved by approximately 1 week of daily exercise training, with near maximal growth observed in male mice with 2 weeks of training; however, female mice were recalcitrant to exercise-induced cardiac growth and required a higher daily intensity of exercise training to achieve significant, albeit modest, increases in cardiac mass. We also found that increases in the energy charge of adenylate and guanylate nucleotide pools precede exercise-induced changes in cardiac size and were associated with higher glucose tracer enrichment in the TCA pool and in amino acids (aspartate, glutamate) sourced by TCA intermediates. Our data also indicate that the activity of collateral biosynthetic pathways of glucose metabolism may not be markedly altered by exercise. Overall, this study provides evidence that metabolic remodeling in the form of heightened energy charge and increased TCA cycle activity and cataplerosis precedes cardiac growth caused by exercise training in male mice. [Display omitted] •Treadmill exercise promotes cardiac growth in male FVB/NJ mice during the first two weeks of training•Female FVB/NJ mice require a higher exercise training intensity than male mice to elicit marginal cardiac growth•Exercise augments energy charge, Krebs cycle activity, and cataplerosis before and during active cardiac growth•Differences in metabolism caused by exercise recede upon establishment of the cardiac growth phenotype
ISSN:0022-2828
1095-8584