{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:33:26Z","timestamp":1793504006292,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Polycystic ovarian syndrome (PCOS) is a multifaceted metabolic and hormonal disorder in females of reproductive age, frequently associated with cardiac disturbances. This research aimed to explore the protective potential of adropin and\/or tirzepatide (Tirze) on cardiometabolic aberrations in the letrozole-induced PCOS model. Female Wistar non-pregnant rats were allotted into five groups: CON; PCOS; PCOS + adropin; PCOS + Tirze; and PCOS + adropin+ Tirze. The serum sex hormones, glucose, and lipid profiles were securitized. Cardiac phosphorylated levels of AKT(pAKT), glycogen synthase kinase-3 beta (pGSK-3\u03b2), NOD-like receptor family pyrin domain containing 3 (NLPR3), IL-1\u03b2 and IL-18 were assayed. The cardiac redox status and endoplasmic reticulum stress (ER) parameters including relative glucose-regulated protein 78 (GRP78) and C\/EBP homologous protein (CHOP) gene expressions were detected. Finally, the immunoreactivity of cardiac NF-\u03baB, Bcl2, and BAX were assessed. Our results displayed that adropin and\/or Tirze intervention successfully alleviated the PCOS-provoked cardiometabolic derangements with better results recorded for the combination treatment. The synergistic effect of adropin and Tirze is mostly mediated via activating the cardiac Akt, which dampens the GSK3\u03b2\/NF-\u03baB\/NLRP3 signaling pathway, with a sequel of alleviating oxidative damage, inflammatory response, ER stress, and related apoptosis, making them alluring desirable therapeutic targets in PCOS-associated cardiac complications.<\/jats:p>","DOI":"10.3390\/ijms26010001","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T02:50:56Z","timestamp":1735008656000},"page":"1","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Adropin\/Tirzepatide Combination Mitigates Cardiac Metabolic Aberrations in a Rat Model of Polycystic Ovarian Syndrome, Implicating the Role of the AKT\/GSK3\u03b2\/NF-\u03baB\/NLRP3 Pathway"],"prefix":"10.3390","volume":"26","author":[{"given":"Islam Ibrahim","family":"Hegab","sequence":"first","affiliation":[{"name":"Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"},{"name":"Bio-Physiology Department, Ibn Sina National College for Medical Studies, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemat El-sayed","family":"El-Horany","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"},{"name":"Department of Biochemistry, College of Medicine, Ha\u2019il University, Hail 81158, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania Nagi","family":"Abd-Ellatif","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7183-6046","authenticated-orcid":false,"given":"Nahla Anas","family":"Nasef","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa H.","family":"Okasha","sequence":"additional","affiliation":[{"name":"Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa Nagy","family":"Emam","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"},{"name":"Bio-Physiology Department, Ibn Sina National College for Medical Studies, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Hassan","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walaa S.","family":"Elseady","sequence":"additional","affiliation":[{"name":"Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa A.","family":"Radwan","sequence":"additional","affiliation":[{"name":"Anatomy and Embryology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha Osama","family":"ElEsawy","sequence":"additional","affiliation":[{"name":"Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser Mostafa","family":"Hafez","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha Elsayed","family":"Hassan","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran Mostafa","family":"Mansour","sequence":"additional","affiliation":[{"name":"Cardiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8305-6196","authenticated-orcid":false,"given":"Gamaleldien Elsayed","family":"Abdelkader","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Basic Medical Sciences, Faculty of Dentistry, University of Petra, Amman 11196, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Fouda","sequence":"additional","affiliation":[{"name":"Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2357-0166","authenticated-orcid":false,"given":"Amira M.","family":"Abd El Maged","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine, Menoufia University, Shebin El Kom 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan M.","family":"Abdallah","sequence":"additional","affiliation":[{"name":"Physiology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1161\/CIRCULATIONAHA.123.065827","article-title":"Polycystic Ovary Syndrome Fuels Cardiovascular Inflammation and Aggravates Ischemic Cardiac 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