Integrative Mechanisms of Metabolic Plasticity: From Nutritional and Epigenetic Modulation to Cardiometabolic and Respiratory Outcomes across the Life Course

Metabolic plasticity lies at the heart of how organisms regulate energy balance and adapt to physiological stress throughout the life course. Disruptions in this adaptive capacity –stemming from both genetic and environmental exposures– can set the stage for maladaptive metabolic responses, increasing risk for cardiometabolic and respiratory dysfunction. Recent research highlights the importance of early-life factors, including maternal nutrition, placental environment, and postnatal exposures, which can “program” metabolic set-points via durable changes in gene expression, mitochondrial function, and tissue crosstalk. Central to this programming are epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, alongside physiological inputs like nutrient availability, inflammation, and neuroendocrine signaling. Despite significant progress, the complex interplay among these factors –particularly how they shape lifelong risk for insulin resistance, endothelial dysfunction, and organ compromise– remains incompletely understood, requiring integrative models that bridge developmental and systems biology with clinical outcomes.This Research Topic aims to synthesize nutritional, epigenetic, and physiological perspectives to elucidate how metabolic plasticity is established, maintained, or disrupted from early development through adult life. By assembling mechanistic, translational, and clinical evidence, this collection seeks to pinpoint the pathways and sensitive windows in which interventions can alter disease trajectories. Emphasis will be placed on identifying modifiable factors and actionable biomarkers that can inform both prevention and targeted therapies for cardiometabolic and respiratory disease. Researchers are encouraged to address questions of causality, heterogeneity, and sex-specific effects, as well as to propose new frameworks that integrate knowledge across traditionally distinct fields.The scope of this Research Topic encompasses the continuum from molecular and cellular mechanisms to whole-organism physiology and disease but focuses on how early-life and lifelong exposures interact to affect metabolic health. Submissions may range from basic research and multi-omics analyses to human studies and intervention trials. To foster deeper understanding, we welcome original research, review and perspective articles addressing, but not limited to, the following themes:- Early-life programming of metabolic flexibility and later cardiometabolic/respiratory outcomes (DOHaD framework)- Epigenetic regulation of metabolic pathways across life stages and tissues- Mitochondrial bioenergetics, oxidative stress, and redox signaling in metabolic remodeling- Endocrine and neuroendocrine control of metabolic set-points (e.g., glucocorticoids, thyroid axis, adipokines)- Circadian rhythms, sleep disruption, and time-of-feeding effects on cardiometabolic and pulmonary physiology- Immunometabolism, inflammation resolution, and tissue remodeling in obesity, diabetes, and airway/lung disease- Nutrition quality, dietary patterns, micronutrients, and targeted supplementation as modulators of plasticity- Exercise and cardiorespiratory fitness as integrative regulators of metabolic flexibility and ventilatory control- Microbiome-derived metabolites and gut–heart/gut–lung axes in metabolic and respiratory comorbidity- Biomarkers, multi-omics integration, and causal inference approaches to identify pathways and risk phenotypes Topic editors: JOAO HENRIQUE COSTA-SILVA, Carol Gois Leandro Source: https://www.frontiersin.org/research-topics/79142/integrative-mechanisms-of-metabolic-plasticity-from-nutritional-and-epigenetic-modulation-to-cardiometabolic-and-respiratory-outcomes-across-the-life-course