Temporal dynamics of weight loss, metabolic reprogramming, and cardiac remodeling: insights from untargeted metabolomic

Abstract Background/Introduction Obesity contributes to maladaptive cardiac remodeling through metabolic dysfunction. Bariatric surgery improves cardiometabolic health and offers a unique human model of rapid cardiometabolic recalibration but the coordinated time-course linking metabolic reprogramming to cardiac structural recovery is not fully defined. Purpose To characterize over 24 weeks changes in weight, metabolic pathways, and cardiac remodeling after bariatric surgery using integrated echocardiography and untargeted metabolomics. Methods Adults with severe obesity underwent clinical evaluation, echocardiography, and plasma untargeted metabolomics at baseline, 4, 12 and 24 weeks post-surgery. Echocardiographic variables included basic parameters and myocardial geometry indices. Metabolomic spectra were analysed using multivariate modelling and pathway enrichment. Associations between metabolic shifts and cardiac remodeling were examined through paired analyses and correlation matrices. Results Participants exhibited substantial weight loss accompanied by significant improvement in myocardial geometry. Metabolomics revealed a marked reprogramming of circulating metabolites, with modulation of lipid oxidation, amino-acid metabolism, and intermediates linked to mitochondrial energetic efficiency. Distinct metabolite clusters correlated with the magnitude of reverse remodeling, indicating coordinated physiological adaptations. Integrated pathway analyses identified metabolic signatures predictive of cardiac structural improvement. Conclusion(s) Bariatric surgery induces coherent metabolic and cardiac benefits that unfold over a 24 week trajectory. Integration of metabolomics with cardiac imaging highlights mechanistic links between improved metabolic flexibility and myocardial recovery. These findings support the use of systems-level profiling to identify biological pathways underlying obesity-related cardiac remodeling and to inform targeted cardiometabolic interventions.Baseline metabolomic predictors of earlyFor image description, please refer to the figure legend and surrounding text. Class-specific metabolomic remodeling paFor image description, please refer to the figure legend and surrounding text.