{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:58:01Z","timestamp":1790866681097,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms27188357","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:23:56Z","timestamp":1790864636000},"page":"8357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipocyte Ferroptosis in Obesity: Molecular Mechanisms and Nutraceutical Perspectives"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0401-4027","authenticated-orcid":false,"given":"Stefano","family":"Ruga","sequence":"first","affiliation":[{"name":"Department of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Matarese","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0186-610X","authenticated-orcid":false,"given":"Antea Maria Pia","family":"Mangano","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4154-8219","authenticated-orcid":false,"given":"Chiara","family":"Lamesta","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Dimatteo","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Miscio","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0587-8467","authenticated-orcid":false,"given":"Canio","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilena","family":"Lauriola","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7759-2141","authenticated-orcid":false,"given":"Renato","family":"Lombardi","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5959-016X","authenticated-orcid":false,"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Sbarro Health Research Organization ETS, 10060 Candiolo, Italy"},{"name":"Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3031-345X","authenticated-orcid":false,"given":"Giovanna","family":"Liguori","sequence":"additional","affiliation":[{"name":"Local Health Authority of Foggia (ASL Foggia), 71121 Foggia, Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA"},{"name":"Sbarro Health Research Organization ETS, 10060 Candiolo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nature05485","article-title":"Inflammation and metabolic disorders","volume":"444","author":"Hotamisligil","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1146\/annurev-immunol-031210-101322","article-title":"Inflammatory mechanisms in obesity","volume":"29","author":"Gregor","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.cmet.2013.06.016","article-title":"Fibrosis and adipose tissue dysfunction","volume":"18","author":"Sun","year":"2013","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41580-018-0093-z","article-title":"Adipogenesis and metabolic health","volume":"20","author":"Ghaben","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.plefa.2005.04.010","article-title":"The adipose organ","volume":"73","author":"Cinti","year":"2005","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1172\/JCI45887","article-title":"Adipose tissue remodeling and obesity","volume":"121","author":"Sun","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/ijo.2008.229","article-title":"Emerging role of adipose tissue hypoxia in obesity and insulin resistance","volume":"33","author":"Ye","year":"2009","journal-title":"Int. J. Obes."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1079\/BJN20041213","article-title":"Adipokines: Inflammation and the pleiotropic role of white adipose tissue","volume":"92","author":"Trayhurn","year":"2004","journal-title":"Br. J. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1172\/JCI20514","article-title":"Obesity-induced inflammatory changes in adipose tissue","volume":"112","author":"Wellen","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1172\/JCI200319451","article-title":"Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance","volume":"112","author":"Xu","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1172\/JCI200319246","article-title":"Obesity is associated with macrophage accumulation in adipose tissue","volume":"112","author":"Weisberg","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1146\/annurev-physiol-021909-135846","article-title":"Macrophages, inflammation, and insulin resistance","volume":"72","author":"Olefsky","year":"2010","journal-title":"Annu. Rev. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1172\/JCI57132","article-title":"Inflammatory links between obesity and metabolic disease","volume":"121","author":"Lumeng","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1194\/jlr.M500294-JLR200","article-title":"Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans","volume":"46","author":"Cinti","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.2337\/db06-0133","article-title":"Increased infiltration of macrophages in omental adipose tissue is associated with marked hepatic lesions in morbid human obesity","volume":"55","author":"Cancello","year":"2006","journal-title":"Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.2337\/diabetes.54.8.2277","article-title":"Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss","volume":"54","author":"Cancello","year":"2005","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, biology and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1080\/15548627.2020.1810918","article-title":"Ferroptosis: Machinery and regulation","volume":"17","author":"Chen","year":"2021","journal-title":"Autophagy"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/jcmm.17701","article-title":"Narrative review of ferroptosis in obesity","volume":"27","author":"He","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1052699","DOI":"10.1155\/2022\/1052699","article-title":"Research Progress of Ferroptosis in Adiposity-Based Chronic Disease (ABCD)","volume":"2022","author":"Du","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.cmet.2024.11.010","article-title":"Adipocyte-derived ferroptotic signaling mitigates obesity","volume":"37","author":"Wang","year":"2025","journal-title":"Cell Metab."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lesjak, M., Simin, N., and Srai, S.K. (2022). Can polyphenols inhibit ferroptosis?. Antioxidants, 11.","DOI":"10.3390\/antiox11010150"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"105580","DOI":"10.1016\/j.phrs.2021.105580","article-title":"Regulation of ferroptosis by bioactive phytochemicals: Implications for medical nutritional therapy","volume":"168","author":"Zheng","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature13148","article-title":"Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy","volume":"509","author":"Mancias","year":"2014","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy promotes ferroptosis by degradation of ferritin","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1038\/s41580-024-00703-5","article-title":"The cell biology of ferroptosis","volume":"25","author":"Dixon","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S2213-8587(13)70174-8","article-title":"Effects of iron overload on chronic metabolic diseases","volume":"2","author":"Manco","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13647","DOI":"10.1111\/obr.13647","article-title":"Iron: The silent culprit in your adipose tissue","volume":"25","year":"2024","journal-title":"Obes. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1101\/gad.314674.118","article-title":"Regulation of lipid peroxidation and ferroptosis in diverse species","volume":"32","author":"Conrad","year":"2018","journal-title":"Genes Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1159\/000243791","article-title":"The role of hepcidin in iron metabolism","volume":"122","author":"Nemeth","year":"2009","journal-title":"Acta Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.bbamcr.2012.01.014","article-title":"Hepcidin and iron homeostasis","volume":"1823","author":"Ganz","year":"2012","journal-title":"Biochim. Biophys. Acta-Mol. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/ajh.26001","article-title":"Cell-type-specific insights into iron regulatory processes","volume":"96","author":"Silvestri","year":"2021","journal-title":"Am. J. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2016.12.034","article-title":"A red carpet for iron metabolism","volume":"168","author":"Muckenthaler","year":"2017","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1182\/blood-2018-06-815894","article-title":"Liver iron sensing and body iron homeostasis","volume":"133","author":"Wang","year":"2019","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41366-023-01299-0","article-title":"Iron, glucose and fat metabolism and obesity: An intertwined relationship","volume":"47","author":"Hilton","year":"2023","journal-title":"Int. J. Obes."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1007\/s13679-024-00600-0","article-title":"Iron-Mediated regulation in adipose tissue: A comprehensive review of metabolism and physiological effects","volume":"14","author":"Yang","year":"2025","journal-title":"Curr. Obes. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/eji.200939889","article-title":"Differential regulation of iron homeostasis during human macrophage polarized activation","volume":"40","author":"Recalcati","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.3324\/haematol.2010.023879","article-title":"Polarization dictates iron handling by inflammatory and alternatively activated macrophages","volume":"95","author":"Corna","year":"2010","journal-title":"Haematologica"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e10308","DOI":"10.7554\/eLife.10308","article-title":"Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis","volume":"4","author":"Mancias","year":"2015","journal-title":"eLife"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Di Lorenzo, R., Marzetti, E., Coelho-Junior, H.J., Calvani, R., Pesce, V., Landi, F., Leeuwenburgh, C., and Picca, A. (2025). Iron metabolism and muscle aging: Where ferritinophagy meets mitochondrial quality control. Cells, 14.","DOI":"10.3390\/cells14090672"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.molcel.2015.06.011","article-title":"Glutaminolysis and transferrin regulate ferroptosis","volume":"59","author":"Gao","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41422-020-00441-1","article-title":"Ferroptosis: Molecular mechanisms and health implications","volume":"31","author":"Tang","year":"2021","journal-title":"Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41392-020-00428-9","article-title":"Ferroptosis: Mechanisms and links with diseases","volume":"6","author":"Yan","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1038\/s41589-020-0613-y","article-title":"Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducers","volume":"16","author":"Soula","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5826","DOI":"10.7150\/thno.100080","article-title":"Ferroptosis at the nexus of metabolism and metabolic diseases","volume":"14","author":"Li","year":"2024","journal-title":"Theranostics"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhou, D., Lu, P., Mo, X., Yang, B., Chen, T., Yao, Y., Xiong, T., Yue, L., and Yang, X. (2024). Ferroptosis and metabolic syndrome and complications: Association, mechanism, and translational applications. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1248934"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2008.07.005","article-title":"Glutathione peroxidase 4 senses and translates oxidative stress into 12\/15-lipoxygenase dependent-and AIF-mediated cell death","volume":"8","author":"Seiler","year":"2008","journal-title":"Cell Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Schneider","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Huang, C.-D., Luo, T., Zhang, H., Cheng, L.-H., Peng, S.-H., Zhou, X.-W., Cao, L., Chen, F.-Y., He, J.-W., and Chen, C. (2025). Ferroptosis as a potential therapeutic target for obesity-related metabolic diseases. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1581632"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.molcel.2018.10.042","article-title":"Role of mitochondria in ferroptosis","volume":"73","author":"Gao","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/s41586-019-1705-2","article-title":"The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis","volume":"575","author":"Bersuker","year":"2019","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41586-019-1707-0","article-title":"FSP1 is a glutathione-independent ferroptosis suppressor","volume":"575","author":"Doll","year":"2019","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1021\/acscentsci.9b01063","article-title":"GTP cyclohydrolase 1\/tetrahydrobiopterin counteract ferroptosis through lipid remodeling","volume":"6","author":"Kraft","year":"2019","journal-title":"ACS Cent. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1080\/03602530600971974","article-title":"Mechanistic studies of the Nrf2-Keap1 signaling pathway","volume":"38","author":"Zhang","year":"2006","journal-title":"Drug Metab. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00204-011-0674-5","article-title":"The cytoprotective role of the Keap1\u2013Nrf2 pathway","volume":"85","author":"Baird","year":"2011","journal-title":"Arch. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.abb.2016.08.005","article-title":"Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants","volume":"617","author":"Kostov","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101107","DOI":"10.1016\/j.redox.2019.101107","article-title":"NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis","volume":"23","author":"Dodson","year":"2019","journal-title":"Redox Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.freeradbiomed.2018.10.426","article-title":"Nrf2 inhibition reverses resistance to GPX4 inhibitor-induced ferroptosis in head and neck cancer","volume":"129","author":"Shin","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.cmet.2020.10.011","article-title":"The metabolic underpinnings of ferroptosis","volume":"32","author":"Zheng","year":"2020","journal-title":"Cell Metab."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2337\/db13-0213","article-title":"Obesity alters adipose tissue macrophage iron content and tissue iron distribution","volume":"63","author":"Orr","year":"2014","journal-title":"Diabetes"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12944-020-01342-3","article-title":"A review on the biology and properties of adipose tissue macrophages involved in adipose tissue physiological and pathophysiological processes","volume":"19","author":"Li","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.2337\/db08-0872","article-title":"Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes","volume":"57","author":"Lumeng","year":"2008","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41571-020-00462-0","article-title":"Broadening horizons: The role of ferroptosis in cancer","volume":"18","author":"Chen","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/nm.4146","article-title":"On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver","volume":"22","author":"Theurl","year":"2016","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s00424-017-1944-8","article-title":"\u201cPumping iron\u201d\u2014How macrophages handle iron at the systemic, microenvironmental, and cellular levels","volume":"469","author":"Nairz","year":"2017","journal-title":"Pfl\u00fcg. Arch.-Eur. J. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhang, S., Sun, Z., Jiang, X., Lu, Z., Ding, L., Li, C., Tian, X., and Wang, Q. (2022). Ferroptosis increases obesity: Crosstalk between adipocytes and the neuroimmune system. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1049936"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"107417","DOI":"10.1016\/j.phrs.2024.107417","article-title":"Targeting leptin\/CCL3-CCL4 axes in NAFLD\/MAFLD: A novel role for BPF in counteracting thalamic inflammation and white matter degeneration","volume":"209","author":"Cardamone","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Nucera, S., Bulotta, R.M., Ruga, S., Caminiti, R., Serra, M., Bava, R., Castagna, F., Lupia, C., Marrelli, M., and Conforti, F. (2023). Natural products for the treatment of non-alcoholic fatty liver disease: A comprehensive review. Sci. Pharm., 91.","DOI":"10.3390\/scipharm91040053"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Menon, V.P., and Sudheer, A.R. (2007). Antioxidant and anti-inflammatory properties of curcumin. The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer.","DOI":"10.1007\/978-0-387-46401-5_3"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Cruz-Gregorio, A., and Aranda-Rivera, A.K. (2023). Quercetin and ferroptosis. Life, 13.","DOI":"10.3390\/life13081730"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Carresi, C., Gliozzi, M., Musolino, V., Scicchitano, M., Scarano, F., Bosco, F., Nucera, S., Maiuolo, J., Macr\u00ec, R., and Ruga, S. (2020). The effect of natural antioxidants in the development of metabolic syndrome: Focus on bergamot polyphenolic fraction. Nutrients, 12.","DOI":"10.3390\/nu12051504"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2018.08.012","article-title":"Astaxanthin: A mechanistic review on its biological activities and health benefits","volume":"136","author":"Fakhri","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Aggarwal, B.B., Surh, Y.-J., and Shishodia, S. (2007). The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease, Springer Science & Business Media.","DOI":"10.1007\/978-0-387-46401-5"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e70384","DOI":"10.1002\/jbt.70384","article-title":"Molecular Alterations in Ferroptosis and the Effects of Resveratrol: A Systematic Review","volume":"39","author":"Carletti","year":"2025","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/S0278-6915(99)00082-4","article-title":"Antioxidant functions of sulforaphane: A potent inducer of Phase II detoxication enzymes","volume":"37","author":"Fahey","year":"1999","journal-title":"Food Chem. Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Angeloni, C., Malaguti, M., Barbalace, M.C., and Hrelia, S. (2017). Bioactivity of olive oil phenols in neuroprotection. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112230"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Cicero, A.F., and Baggioni, A. (2016). Berberine and its role in chronic disease. Anti-Inflammatory Nutraceuticals and Chronic Diseases, Springer.","DOI":"10.1007\/978-3-319-41334-1_2"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2073S","DOI":"10.1093\/jn\/130.8.2073S","article-title":"Dietary intake and bioavailability of polyphenols","volume":"130","author":"Scalbert","year":"2000","journal-title":"J. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Cory, H., Passarelli, S., Szeto, J., Tamez, M., and Mattei, J. (2018). The role of polyphenols in human health and food systems: A mini-review. Front. Nutr., 5.","DOI":"10.3389\/fnut.2018.00087"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Caminiti, R., Carresi, C., Mollace, R., Macr\u00ec, R., Scarano, F., Oppedisano, F., Maiuolo, J., Serra, M., Ruga, S., and Nucera, S. (2024). The potential effect of natural antioxidants on endothelial dysfunction associated with arterial hypertension. Front. Cardiovasc. Med., 11.","DOI":"10.3389\/fcvm.2024.1345218"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A review of its effects on human health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Scarano, F., Gliozzi, M., Zito, M.C., Guarnieri, L., Carresi, C., Macr\u00ec, R., Nucera, S., Scicchitano, M., Bosco, F., and Ruga, S. (2021). Potential of nutraceutical supplementation in the modulation of white and brown fat tissues in obesity-associated disorders: Role of inflammatory signalling. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073351"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e70252","DOI":"10.1002\/mco2.70252","article-title":"Resveratrol: Molecular mechanisms, health benefits, and potential adverse effects","volume":"6","author":"Ren","year":"2025","journal-title":"MedComm"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"He, Y., Li, M., Wang, Z., Pan, C., Lan, X., and Guan, W. (2026). Phloretin Protects Goat Adipose-Derived Mesenchymal Stem Cells Against Ferroptosis by Regulating the Nrf2\/HO-1\/GPX4 Signaling Pathway. Animals, 16.","DOI":"10.3390\/ani16091286"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.lfs.2017.12.005","article-title":"Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy","volume":"194","author":"Kashyap","year":"2018","journal-title":"Life Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1055\/s-0028-1088314","article-title":"Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin","volume":"74","author":"Seelinger","year":"2008","journal-title":"Planta Medica"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1038\/s41598-020-59485-3","article-title":"Bergamot polyphenols improve dyslipidemia and pathophysiological features in a mouse model of non-alcoholic fatty liver disease","volume":"10","author":"Musolino","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Nucera, S., Scarano, F., Macr\u00ec, R., Mollace, R., Gliozzi, M., Carresi, C., Ruga, S., Serra, M., Tavernese, A., and Caminiti, R. (2023). The effect of an innovative combination of bergamot polyphenolic fraction and Cynara Cardunculus L. extract on weight gain reduction and fat browning in obese mice. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25010191"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Maiuolo, J., Mollace, R., Bosco, F., Scarano, F., Oppedisano, F., Nucera, S., Ruga, S., Guarnieri, L., Macri, R., and Bava, I. (2023). The phytochemical synergistic properties of combination of bergamot polyphenolic fraction and Cynara cardunculus extract in non-alcoholic fatty liver disease. Agriculture, 13.","DOI":"10.3390\/agriculture13020249"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Maiuolo, J., Bonacci, S., Ruga, S., Bosco, F., Guarnieri, L., Leo, A., Citraro, R., Ragusa, S., Palma, E., and Mollace, V. (2024). Two Olea europea extracts reduce deleterious effects induced by lead exposure in a model of neurotoxicity: Involvement of the endoplasmic reticulum. Res. Sq.","DOI":"10.21203\/rs.3.rs-4053465\/v1"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1002\/ptr.6252","article-title":"Berberine and barberry (Berberis vulgaris): A clinical review","volume":"33","author":"Imenshahidi","year":"2019","journal-title":"Phytother. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"118304","DOI":"10.1016\/j.biopha.2025.118304","article-title":"Targeting ferroptosis with natural products: Investigating promising agents for treating diabetes and its complications","volume":"189","author":"He","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4658","DOI":"10.1002\/ptr.70083","article-title":"Natural products targeting ferroptosis in type 2 diabetes mellitus and its complications","volume":"39","author":"Niazpour","year":"2025","journal-title":"Phytother. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"415078","DOI":"10.1155\/2013\/415078","article-title":"Sulforaphane as a potential protective phytochemical against neurodegenerative diseases","volume":"2013","author":"Tarozzi","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1021\/jf980049c","article-title":"Olive oil phenols and their potential effects on human health","volume":"46","author":"Visioli","year":"1998","journal-title":"J. Agric. Food Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1080\/21623945.2018.1469942","article-title":"The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans","volume":"7","author":"Most","year":"2018","journal-title":"Adipocyte"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1016\/j.cell.2022.06.003","article-title":"Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications","volume":"185","author":"Stockwell","year":"2022","journal-title":"Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:27:33Z","timestamp":1790864853000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":103,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188357"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188357","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}