Metabolomics-constrained modelling reveals dominant oxidative metabolism in the Egyptian fruit bat myocardium

Aim The present study aimed to elucidate which pathways contribute to cardiometabolic adaptation in Egyptian fruit bats. Methods Utilising cardiac tissues from Egyptian fruit bats ( Rousettus aegyptiacus ) and C57BL/6J mice, we combined liquid chromatography-mass spectrometry metabolic profiling, non-targeted ¹H NMR spectroscopy, and in silico computational modelling using the genome-scale mammalian network CardioNet. By integrating complementary untargeted and targeted metabolomics with genome-scale flux balance analysis, this approach enables systems-level inference of pathway activity beyond static metabolite abundance measurements. Main findings Our analyses revealed that bat hearts exhibit a distinct metabolic profile characterised by depleted glycogen reserves and increased reliance on lipid oxidation to meet energy demands. Notably, bat hearts displayed elevated fluxes in oxidative phosphorylation, β-oxidation of long-chain fatty acids, and the Krebs cycle, alongside reduced amino acid catabolism. These findings suggest that bats have evolved unique metabolic strategies to support the high-energy demands of flight, maintaining cardiac function without succumbing to pathological remodelling. Conclusions This study provides the first comprehensive insight into the metabolic adaptations in the cardiac tissue of a bat species, contributing to our understanding of how these mammals endure extreme physiological stresses.