{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:59:49Z","timestamp":1790398789413,"version":"4.1.0"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry for University and Research","award":["20229WP2JJ CUP D53D23012320006"],"award-info":[{"award-number":["20229WP2JJ CUP D53D23012320006"]}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["MARELI_GFI2_25_01_F"],"award-info":[{"award-number":["MARELI_GFI2_25_01_F"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["BERM_RILO_24_02"],"award-info":[{"award-number":["BERM_RILO_24_02"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"award":["MARELI_GFI2_25_01_F"],"award-info":[{"award-number":["MARELI_GFI2_25_01_F"]}],"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}]},{"award":["BERM_RILO_24_02"],"award-info":[{"award-number":["BERM_RILO_24_02"]}],"id":[{"id":"https:\/\/ror.org\/048tbm396","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic low-grade inflammation (metaflammation) is a key contributor to obesity-associated metabolic disorders and their cardiovascular complications. This study investigated the effects of CXT29, a novel dual cyclooxygenase-2 (COX-2) inhibitor and thromboxane prostanoid receptor (TP) antagonist, in comparison with its parent compound etodolac, in a murine model of diet-induced metabolic dysfunction. Four-week-old male C57BL\/6 mice were fed either a standard diet or a high-fat diet for 18 weeks and subsequently treated with etodolac (20 mg\/kg\/day) or CXT29 (25 mg\/kg\/day) by oral gavage for 5 weeks. High-fat-diet-fed mice developed increased body weight, impaired glucose tolerance, altered circulating metabolic hormones, liver dysfunction, steatosis, inflammatory cell infiltration, and systemic inflammation. Both treatments attenuated systemic inflammation and improved the metabolic alterations induced by the obesogenic diet. Notably, CXT29, but not etodolac, attenuated the increase in circulating plasminogen activator inhibitor-1 (PAI-1), a biomarker associated with cardiovascular risk. These findings indicate that pharmacological inhibition of COX-2 improves metabolic dysfunction associated with diet-induced obesity. Furthermore, the additional TP antagonism provided by CXT29 does not compromise the metabolic benefits associate with COX-2 inhibition, while displaying a distinct effect on circulating PAI-1, supporting further investigation of this dual-target approach in obesity-associated metabolic dysfunction.<\/jats:p>","DOI":"10.3390\/molecules31193403","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:16:28Z","timestamp":1790244988000},"page":"3403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beneficial Effects of a Dual Cyclooxygenase Inhibitor\u2212Thromboxane Antagonist in Counteracting High-Fat Diet-Induced Metaflammation"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2094-8483","authenticated-orcid":false,"given":"Giacomo","family":"Einaudi","sequence":"first","affiliation":[{"name":"Pharmacology Unit, School of Pharmacy, University 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