Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells
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 m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/1/9 |
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| author | Benjamin B. Johnson Johannes Reinhold Terri L. Holmes Jamie A. Moore Verity Cowell Andreia S. Bernardo Stuart A. Rushworth Vassilios Vassiliou James G. W. Smith |
| author_facet | Benjamin B. Johnson Johannes Reinhold Terri L. Holmes Jamie A. Moore Verity Cowell Andreia S. Bernardo Stuart A. Rushworth Vassilios Vassiliou James G. W. Smith |
| author_sort | Benjamin B. Johnson |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T00:59:12Z |
| format | Article |
| id | doaj.art-f4c3611d9fa04f77abfab13369049707 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T00:59:12Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-f4c3611d9fa04f77abfab133690497072023-11-23T14:39:29ZengMDPI AGMetabolites2218-19892021-12-01121910.3390/metabo12010009Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem CellsBenjamin B. Johnson0Johannes Reinhold1Terri L. Holmes2Jamie A. Moore3Verity Cowell4Andreia S. Bernardo5Stuart A. Rushworth6Vassilios Vassiliou7James G. W. Smith8Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKDevelopmental Biology Laboratory, Francis Crick Institute, London NW1 1AT, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKFaculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich NR4 7UQ, UKCardiomyocytes 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.https://www.mdpi.com/2218-1989/12/1/9iron deficiencycardiomyocytespluripotent stem cells |
| spellingShingle | Benjamin B. Johnson Johannes Reinhold Terri L. Holmes Jamie A. Moore Verity Cowell Andreia S. Bernardo Stuart A. Rushworth Vassilios Vassiliou James G. W. Smith Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells Metabolites iron deficiency cardiomyocytes pluripotent stem cells |
| title | Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells |
| title_full | Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells |
| title_fullStr | Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells |
| title_full_unstemmed | Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells |
| title_short | Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human Pluripotent Stem Cells |
| title_sort | modelling metabolic shifts during cardiomyocyte differentiation iron deficiency and transferrin rescue using human pluripotent stem cells |
| topic | iron deficiency cardiomyocytes pluripotent stem cells |
| url | https://www.mdpi.com/2218-1989/12/1/9 |
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