Modelling Metabolic Shifts during Cardiomyocyte Differentiation, Iron Deficiency and Transferrin Rescue Using Human...

Area of Science:

• Cardiovascular Biology
• Cellular Metabolism
• Iron Metabolism

Background:

• Cardiomyocytes have specialized metabolic needs for high energy demand.
• Heart metabolism matures during development, shifting from glycolysis to fatty acid oxidation.
• Iron deficiency (ID) causes cellular metabolism disruptions, but specific alterations are unclear.

Purpose of the Study:

• To investigate metabolic substrate utilization changes in cardiomyocytes during iron deficiency.
• To assess the impact of transferrin rescue on metabolism in iron-deficient cardiomyocytes.
• To identify potential biomarkers and therapeutic targets for cardiovascular diseases related to iron deficiency.

Main Methods:

• Utilized human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM).
• Induced iron deficiency and performed transferrin rescue experiments.
• Analyzed major metabolic substrate utilization, including fatty acid, glycolysis, and TCA cycle pathways.

Main Results:

• Fatty acid metabolism showed the greatest increase during hiPSC-CM differentiation.
• Iron deficiency led to increased reliance on glycolysis and impaired TCA cycle, amino acid, and fatty acid substrates.
• Transferrin rescue partially improved TCA cycle metabolism, but amino acid and fatty acid metabolism remained perturbed.

Conclusions:

• Iron deficiency significantly alters cardiomyocyte substrate metabolism, favoring glycolysis.
• Partial iron replenishment can reverse some adverse metabolic changes.
• Metabolic alterations in iron deficiency present potential targets for cardiovascular disease therapies.