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The novel pan-peroxisome proliferator-activated receptor (PPAR) agonist 1d has been previously shown to alleviate insulin resistance and hepatic steatosis in type 2 diabetic (T2DM) mice; however, its mechanism of action remains unclear. Our integrated in vitro and in vivo findings demonstrate that compound 1d significantly improves disordered hepatic lipid metabolism by modulating the AMPK-ACC-PPAR\u03b1 axis\u2014specifically, by upregulating AMPK expression and phosphorylation, inhibiting ACC activity, downregulating FASN, and upregulating PPAR\u03b1. Concurrently, 1d exhibits potent anti-inflammatory effects in both settings, effectively mitigating hepatic inflammation in a MASH mouse model. Therefore, compound 1d improves lipid metabolism through the AMPK-ACC-PPAR\u03b1 axis and additionally provides an anti-inflammatory benefit, highlighting its potential as a novel therapeutic candidate for MASH.<\/jats:p>","DOI":"10.3390\/ijms262211099","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11099","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Aurone Derivative Ameliorates MASH Lipid Metabolism via the AMPK-ACC-PPAR\u03b1 Axis"],"prefix":"10.3390","volume":"26","author":[{"given":"Sule","family":"Bai","sequence":"first","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Qie","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5582-3309","authenticated-orcid":false,"given":"Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cen","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-1484","authenticated-orcid":false,"given":"Yuou","family":"Teng","sequence":"additional","affiliation":[{"name":"School of Biological Engineering, Tianjin University of Science and Technology, Tianjin 300457, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2023.04.036","article-title":"Changing epidemiology, global trends and implications for outcomes of NAFLD","volume":"79","author":"Wong","year":"2023","journal-title":"J. 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