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Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells

1
Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UK
2
Developmental Biology Laboratory, Francis Crick Institute, London NW1 1AT, UK
3
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
*
Authors to whom correspondence should be addressed.
Denotes joint first author.
Academic Editor: German Perdomo
Metabolites 2022, 12(1), 9; https://doi.org/10.3390/metabo12010009
Received: 28 October 2021 / Revised: 3 December 2021 / Accepted: 20 December 2021 / Published: 22 December 2021
Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases. View Full-Text
Keywords: iron deficiency; cardiomyocytes; pluripotent stem cells iron deficiency; cardiomyocytes; pluripotent stem cells
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MDPI and ACS Style

Johnson, B.B.; Reinhold, J.; Holmes, T.L.; Moore, J.A.; Cowell, V.; Bernardo, A.S.; Rushworth, S.A.; Vassiliou, V.; Smith, J.G.W. Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells. Metabolites 2022, 12, 9. https://doi.org/10.3390/metabo12010009

AMA Style

Johnson BB, Reinhold J, Holmes TL, Moore JA, Cowell V, Bernardo AS, Rushworth SA, Vassiliou V, Smith JGW. Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells. Metabolites. 2022; 12(1):9. https://doi.org/10.3390/metabo12010009

Chicago/Turabian Style

Johnson, Benjamin B., Johannes Reinhold, Terri L. Holmes, Jamie A. Moore, Verity Cowell, Andreia S. Bernardo, Stuart A. Rushworth, Vassilios Vassiliou, and James G.W. Smith. 2022. "Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells" Metabolites 12, no. 1: 9. https://doi.org/10.3390/metabo12010009

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