{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:08:52Z","timestamp":1790172532005,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp;amp; Nutrition"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Peroxisome proliferator\u2010activated receptor gamma (PPAR\u03b3) is a critical therapeutic target for metabolic disorders like non\u2010alcoholic fatty liver disease (NAFLD). However, PPAR\u03b3 full agonists such as rosiglitazone (ROSI) exhibit limited efficacy and off\u2010target effects. Intriguingly, transcriptomic analyses revealed dynamic PPAR\u03b3 expression during NAFLD progression\u2014compensatory upregulation in early stages and downregulation in advanced disease\u2014highlighting the need for novel modulators. This study investigates the therapeutic potential of stachyose (STA), a natural bioactive compound, in NAFLD and its mechanism of action via PPAR\u03b3 modulation. Using structure\u2010based virtual screening of 4531 natural compounds, STA was identified as a PPAR\u03b3\u2010targeted ligand, validated by surface plasmon resonance and molecular docking. Network pharmacology and functional enrichment analyses elucidated STA's multi\u2010target effects. In\u00a0vitro and in\u00a0vivo models assessed STA's impacts on lipid metabolism, inflammation, and insulin resistance. Molecular dynamics simulations and post\u2010translational modification studies clarified STA\u2010PPAR\u03b3 interactions. STA outperformed ROSI in mitigating hepatic lipid accumulation, inflammation, and insulin resistance in both models. STA bound stably to PPAR\u03b3 via residues GLU259, GLY284, PHE287, ILE341, and LEU270, with reduced PPAR\u03b3 acetylation mediated by SIRT1 activation. Unlike ROSI, STA preserved PPAR\u03b3 activity without inhibiting phosphorylation at Ser273, suggesting a distinct mechanism of action. STA emerges as a partial PPAR\u03b3 agonist with superior efficacy and safety profiles compared to ROSI. Its dual role in enhancing fatty acid oxidation and suppressing lipogenesis, coupled with SIRT1\u2010dependent deacetylation of PPAR\u03b3, positions STA as a promising candidate for NAFLD therapy. This study provides a mechanistic foundation for developing PPAR\u03b3\u2010targeted interventions with reduced side effects.<\/jats:p>","DOI":"10.1002\/fsn3.71009","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T05:34:47Z","timestamp":1758605687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Screening Based on Structural and Biological Verification of Stachyose as a\n                    <scp>PPAR\u03b3<\/scp>\n                    \u2010Modulating Ligand for the Treatment of Non\u2010Alcoholic Fatty Liver Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Binbo","family":"Fang","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"School of Medicine Taizhou University  Taizhou Zhejiang 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