Genome-scale modelling and stable isotope tracing reveal dynamic metabolic reprogramming in a human cardiac hypertrophy model

ET-1 stimulation of human iPSC-derived cardiomyocytes shows time-dependent metabolic reprogramming over 8 to 48 hours, including rising glycolytic flux and reduced fatty acid β-oxidation.

• Why it matters: Pathological cardiac hypertrophy involves metabolic remodeling, but its temporal dynamics in human cardiomyocyte models are not well defined.
• What they did: The study integrated RNA sequencing at 8 and 48 hours with Human2.0 genome-scale metabolic modelling and stable isotope-resolved metabolomics using 13C-substrate tracing, then validated fluxes by extracellular flux analysis.
• The result: After 48 hours, extracellular fluxes indicate higher glycolytic capacity and mitochondrial respiration, while 13C tracing shows increased glucose-derived labeling across glycolysis, PPP, serine-glycine, and the TCA cycle, consistent with altered carbon allocation.

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