Adipocyte Ferroptosis in Obesity: Molecular Mechanisms and Nutraceutical Perspectives

The global obesity epidemic underscores the urgent need to dissect the molecular mechanisms driving the transition from benign adipose tissue expansion to pathological dysfunction, with adipocyte death representing a critical tipping point in this process. This narrative review synthesizes evidence from peer-reviewed literature concerning the emerging role of ferroptosis in adipose tissue dysfunction, examining the core molecular machinery of iron-dependent lipid peroxidation, the GPX4-glutathione defense axis, and the Nrf2-Keap1 cytoprotective pathway within the specific context of obese adipose tissue biology. The analysis reveals that the obese adipose microenvironment, characterized by pathological iron accumulation, enrichment of peroxidation-prone polyunsaturated fatty acid-containing phospholipids, and a chronically besieged antioxidant defense network, creates conditions uniquely favorable to ferroptotic execution. Furthermore, available evidence suggests that signals released from ferroptotic adipocytes are likely to promote macrophage polarization toward a pro-inflammatory phenotype, establishing a self-amplifying pathogenic loop that propagates local and systemic metabolic dysregulation. The review identifies multiple plant-derived nutraceuticals, including curcumin, resveratrol, quercetin, bergamot polyphenolic fraction, sulforaphane, oleuropein, and astaxanthin, as promising multi-targeted modulators capable of intercepting the ferroptotic cascade at the levels of iron catalysis, lipid radical propagation, and Nrf2-dependent antioxidant defense potentiation. These findings position adipocyte ferroptosis as a novel therapeutic target in obesity and support the rationale for mechanism-based nutraceutical interventions aimed at protecting the adipose organ from pathological cell death.