Adipocyte Ferroptosis in Obesity: Molecular Mechanisms and Nutraceutical Perspectives
6 affiliations
- 1Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy
- 2Vita-Salute San Raffaele University, 20132 Milan, Italy
- 3Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy
- 4Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
- 5Sbarro Health Research Organization ETS, 10060 Candiolo, Italy
- 6Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy
Abstract
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.
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BibTeX
@article{ruga2026adipocyte,
title = {{Adipocyte Ferroptosis in Obesity: Molecular Mechanisms and Nutraceutical Perspectives}},
author = {Stefano Ruga and Elisa Matarese and Antea Maria Pia Mangano and Chiara Lamesta and Tiziana Dimatteo and Leonardo Miscio and Canio Martinelli and Marilena Lauriola and Renato Lombardi and Antonio Giordano and Giovanna Liguori},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27188357},
url = {https://www.mdpi.com/1422-0067/27/18/8357},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Adipocyte Ferroptosis in Obesity: Molecular Mechanisms and Nutraceutical Perspectives
AU - Stefano Ruga
AU - Elisa Matarese
AU - Antea Maria Pia Mangano
AU - Chiara Lamesta
AU - Tiziana Dimatteo
AU - Leonardo Miscio
AU - Canio Martinelli
AU - Marilena Lauriola
AU - Renato Lombardi
AU - Antonio Giordano
AU - Giovanna Liguori
PY - 2026
DA - 2026/09/19
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27188357
UR - https://www.mdpi.com/1422-0067/27/18/8357
AB - 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.
SN - 1422-0067
ER -