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Triterpenes, known for their diverse pharmacological properties, have shown potential in improving insulin sensitivity and exerting antidiabetic and antiobesity effects. This study evaluated the effects of taraxasterol acetate (TXA), a pentacyclic triterpene isolated from Eupatorium ballotaefolium, on TNF-\u03b1-induced insulin resistance and lipolysis in mature 3T3-L1 adipocytes. TXA significantly enhanced glucose uptake in insulin-resistant adipocytes by promoting GLUT4 translocation by activating the IRS-1\/PI3K\/Akt signaling pathway and upregulating AMPK expression. TXA also inhibited NF-\u03baB and JNK signaling, reducing inflammation and mitigated oxidative stress by decreasing intracellular reactive oxygen species (ROS) levels and enhancing antioxidant enzyme activity, including superoxide dismutase (SOD) and catalase (CAT). Moreover, TXA normalized adipokine secretion by increasing leptin and adiponectin levels, and promoted lipid accumulation through the modulation of PPAR\u03b3, HSL, ATGL, and Perilipin expression. TXA further improved lipid metabolism by upregulating fatty acid \u03b2-oxidation genes (ACOX1, CPT1b) and supported mitochondrial function by enhancing PGC-1\u03b1 and TFAM expression. Collectively, these findings demonstrate that TXA mitigates TNF-\u03b1-induced insulin resistance by improving insulin signaling, suppressing inflammation and oxidative stress, and improving lipid and mitochondrial metabolism. These results suggest that TXA is a promising therapeutic candidate for the prevention and treatment of insulin resistance and related metabolic disorders.<\/jats:p>","DOI":"10.1021\/acsomega.5c12241","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:57:36Z","timestamp":1772114256000},"page":"15133-15144","source":"Crossref","is-referenced-by-count":0,"title":["Taraxasterol Acetate Attenuates TNF-\u03b1-Induced\nInsulin Resistance via Regulation of Insulin Signaling, Inflammation,\nand Lipid Metabolism in 3T3-L1 Cells"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9653-7037","authenticated-orcid":true,"given":"Renan\nP.","family":"de Lima","sequence":"first","affiliation":[{"name":"Weill Cornell Medicine , , , ,","place":["New York, New York, United States, 10021"]},{"name":"Federal University of Ceara\u0301 , , , ,","place":["Fortaleza, Ceara\u0301, Brazil, 60430-270"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca Tuelly\nB.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , , ,","place":["Fortaleza, Ceara\u0301, Brazil, 60430-270"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Virginia L.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , , ,","place":["Fortaleza, Ceara\u0301, Brazil, 60430-270"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rose Jane\nR.","family":"Albuquerque","sequence":"additional","affiliation":[{"name":"Vale do Acarau\u0301 State University , , ,","place":["Sobral, Ceara\u0301, Brazil, 62010-295"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1617-7586","authenticated-orcid":true,"given":"Oti\u0301lia D. L.","family":"Pessoa","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , , ,","place":["Fortaleza, Ceara\u0301, Brazil, 60440-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3625-8540","authenticated-orcid":true,"given":"Fla\u0301via A.","family":"Santos","sequence":"additional","affiliation":[{"name":"Federal University of Ceara\u0301 , , , ,","place":["Fortaleza, Ceara\u0301, Brazil, 60430-270"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"2026081508095284300_cit1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2021-067516","article-title":"Anthropometric\nand adiposity indicators\nand risk of type 2 diabetes: systematic review and dose-response meta-analysis\nof cohort studies","volume":"376","author":"Jayedi","year":"2022","journal-title":"BMJ"},{"key":"2026081508095284300_cit2","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.semcancer.2023.03.008","article-title":"Excess body weight: Novel insights\ninto its roles in obesity comorbidities","volume":"92","author":"Zhang","year":"2023","journal-title":"Semin.\nCancer Biol."},{"key":"2026081508095284300_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes\nAtlas: Global, regional and country-level diabetes prevalence estimates\nfor 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes\nRes. 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