Immunometabolic Plasticity in Sarcopenic Obesity: Toward a New Paradigm for Precision Immunonutrition

Abstract

Despite decades of research, immunonutrition continues to generate heterogeneous and often contradictory clinical outcomes, suggesting that nutrients do not exert fixed immunological effects but rather interact with the biological context in which they operate. Sarcopenic obesity (SO) represents one of the clearest clinical models of this complexity, where chronic low-grade inflammation, mitochondrial dysfunction, anabolic resistance, metabolic inflexibility, and microbiota remodeling converge to impair the adaptive capacity of immune and metabolic integrated systems. We propose that this condition should be interpreted as a state of impaired immunometabolic plasticity, providing a conceptual framework to explain the context-dependent variability of nutritional responses. Within this perspective, micronutrients are reconsidered not simply as cofactors supporting immune competence, but as dynamic regulators of interconnected immunometabolic pathways. Particular attention is devoted to vitamin D and resveratrol, presented as complementary regulators of immunometabolic plasticity. Whereas vitamin D supports biological competence, resveratrol acts as a higher-order signaling modulator through the the SIRT1/AMPK–PGC-1α axis to influence mitochondrial function, inflammatory tone, metabolic flexibility, and epigenetic adaptation. Beyond isolated compounds, bioactive-rich food matrices, exemplified by Opuntia ficus-indica, are discussed as systems-level modulators capable of coordinating inflammatory, metabolic, redox, and microbiota-dependent biological circuitry. Rather than focusing on nutrient supplementation alone, this review introduces immunometabolic plasticity as a unifying concept linking nutritional signals to immune adaptation across different biological contexts. Finally, we discuss how biomarker-guided phenotyping, multi-omics integration, and context-aware nutritional interventions may establish the basis for precision immunonutrition, shifting the field from generalized supplementation strategies toward restoration of adaptive immunometabolic resilience.