Intracellular sodium elevation reprograms cardiac metabolism: Metabolomics data

<p><span><span><span><span><span><span><span><span><span><span><span>Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodeling occurs. We assessed whether acute (75μM ouabain 100nM blebbistatin) and chronic myocardial Na_iload (PLM^3SAmouse) are causally linked to metabolic remodeling and whether the hypertrophied failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLM^WT), transgenic (PLM^3SA), ouabain treated and hypertrophied Langendorff-perfused mouse hearts were studied by ²³Na, ³¹P, ¹³C NMR followed by ¹H NMR metabolomic profiling. Elevated Na_i leads to <i><u>common </u></i>adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorated the metabolic changes. <i>In silico</i> modelling indicated altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Na_i overload or inhibition of Na/Ca_mitomay be a new approach to ameliorate metabolic dysregulation in heart failure.</span></span></span></span></span></span></span></span></span></span></span></p>