{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:14:27Z","timestamp":1789035267709,"version":"build-2803163510"},"reference-count":67,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Metabolic syndrome (MetS) is associated with ectopic fat deposition, chronic systemic inflammation, oxidative stress, and increased susceptibility to organ dysfunction. While its cardiovascular consequences have been extensively studied, pulmonary al-terations remain less well characterized, particularly with respect to ferropto-sis-regulatory pathways. In this study, we evaluated ectopic fat deposition, TLR4\/NF-\u03baB signaling pathway, and ferroptosis-regulatory markers in a MetS rat model and analyzed the therapeutic potential of combined resveratrol plus quercetin (combined R + Q) supplementation. Rats were maintained for five months with 30% sucrose in drinking water to induce MetS and subsequently treated for 4 weeks with the R + Q combination (50 and 0.95 mg\/kg\/day, respectively). Lung tissue was analyzed by fluorescence microscopy to assess fat deposition, by colorimetric histology to evaluate hemosiderin-containing cells, including the quantification of hemosiderin-laden macrophages (HLMs), and by immunoblotting to determine TLR4, p-p65, and glutathione peroxidase 4 (GPX4), as well as cystine\/glutamate antiporter SLC7A11 (xCT) protein expression. Lungs from MetS rats exhibited significantly higher fat deposits, pathological HLMs accumulation, upregulated TLR4\/p-p65 signaling, elevated compensatory GPX4 expression, and depressed xCT levels compared with controls. Notably, the combined R + Q treatment markedly attenuated alterations in TLR4\/NF-\u03baB signaling and successfully restored xCT expression (p = 0.0116), stabilizing pulmonary redox homeostasis and limiting overall tissue susceptibility to lipotoxic injury.<\/jats:p>","DOI":"10.3390\/cimb48090913","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:30:02Z","timestamp":1788798602000},"page":"913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Syndrome-Associated Pulmonary Lipid and Iron Accumulation and Alterations in TLR4\/NF-\u03baB Signaling and Ferroptosis-Regulatory Proteins Are Attenuated by Resveratrol Plus Quercetin in Rats"],"prefix":"10.3390","volume":"48","author":[{"given":"Mar\u00eda Esther","family":"Rubio-Ru\u00edz","sequence":"first","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6703-2176","authenticated-orcid":false,"given":"Agustina","family":"Cano-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena Alejandra","family":"M\u00e9ndez-Castro","sequence":"additional","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzel Yoandra","family":"Varona-Ya\u00f1ez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3600-249X","authenticated-orcid":false,"given":"Elizabeth","family":"Carre\u00f3n-Torres","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eulises","family":"D\u00edaz-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Reproductive Biology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Vasco de Quiroga 15, Secci\u00f3n XVI, Tlalpan, Mexico City 14000, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda del Pilar","family":"Ramos-Godinez","sequence":"additional","affiliation":[{"name":"Department of Electron Microscopy, Instituto Nacional de Cancerolog\u00eda, San Fernando No. 22, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Criselda","family":"Mendoza-Milla","sequence":"additional","affiliation":[{"name":"Research Unit, Signal Transduction Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Calzada de Tlalpan 4502, Belisario Dom\u00ednguez Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0077-5079","authenticated-orcid":false,"given":"Alfredo","family":"Cruz-Gregorio","sequence":"additional","affiliation":[{"name":"Department of Physiology, Instituto Nacional de Cardiolog\u00eda Ignacio Ch\u00e1vez, Juan Badiano 1, Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. 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