{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:52Z","timestamp":1787027872353,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Chenzhou National Sustainable Development Agenda Innovation Demonstration Zone Construction Project","award":["2023sfq38"],"award-info":[{"award-number":["2023sfq38"]}]},{"DOI":"10.13039\/501100002767","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2024JJ5180"],"award-info":[{"award-number":["2024JJ5180"]}],"id":[{"id":"10.13039\/501100002767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Dysregulated lipid metabolism is a core pathogenic driver of type 2 diabetes. Honokiol (HKL), the major bioactive constituent of Magnolia officinalis, possesses anti-diabetic and lipid-regulatory properties. However, the underlying molecular mechanism remains elusive. This study investigates how HKL ameliorates high-glucose\/high-fat (HGHF)-induced hepatic lipid accumulation, with a focus on the role of SIRT3-mediated deacetylation of peroxisome proliferator-activated receptor \u03b3 (PPARG). The core targets of HKL were identified through network pharmacology and molecular docking. Human hepatic MIHA cells were treated with glucose (Glu, 40 mM) and palmitic acid (0.2~0.3 mM PA) to establish a lipid accumulation model, followed by treatment with HKL (5\u201310 \u03bcM) with or without a confirmed selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP). Lipid accumulation was assessed by Oil Red O staining and by measuring triglyceride (TG) and total cholesterol (TC) levels. Protein expression and the SIRT3-PPARG interaction were analyzed by Western blot and co-immunoprecipitation (Co-IP). SIRT3 and PPARG were identified as core targets of HKL, exhibiting strong binding with calculated energies of \u22126.834 and \u22126.579 kcal\/mol, respectively. In MIHA cells, HGHF (40 mM Glu + 0.2\u20130.3 mM PA) induced lipid accumulation, including increased lipid droplets, and elevated TG (2.5\u20133.2-fold) and TC (2.2\u20132.8-fold) contents in a dose-dependent manner, accompanied by downregulated SIRT3\/PPARG expression and heightened global protein acetylation. The non-cytotoxic HGHF-M condition (40 mM Glu + 0.2 mM PA) was selected for further experiments. HKL (5\u201310 \u03bcM) dose-dependently reduced lipid accumulation by ~38\u201360%, decreased TG and TC levels by up to ~13% and ~30%, and restored SIRT3\/PPARG expression. The protective effects of HKL were reversed by inhibition of SIRT3 with 3-TYP. Co-IP confirmed the interaction between SIRT3 and PPARG, and SIRT3 overexpression significantly decreased the acetylation level of PPARG. This study suggests that HKL ameliorates hepatic lipid accumulation via SIRT3-mediated deacetylation of PPARG, providing an experimental basis for considering HKL as a potential therapeutic agent against metabolic disorders.<\/jats:p>","DOI":"10.3390\/cells15121095","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:58:38Z","timestamp":1781661518000},"page":"1095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Honokiol Ameliorates Hepatic Lipid Accumulation by Deacetylating PPARG via SIRT3"],"prefix":"10.3390","volume":"15","author":[{"given":"Yantao","family":"Yang","sequence":"first","affiliation":[{"name":"College of Horticulture, Hunan Agricultural University, Changsha 410128, China"},{"name":"State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxiang","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Horticulture, Hunan Agricultural University, Changsha 410128, China"},{"name":"State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Horticulture, Hunan Agricultural University, Changsha 410128, China"},{"name":"State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbo","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Horticulture, Hunan Agricultural University, Changsha 410128, China"},{"name":"State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China"},{"name":"Hunan Provincial Engineering Research Center of Medical Nutrition Intervention Technology for Metabolic Diseases, Hunan Agricultural University, Changsha 410128, China"},{"name":"National Research Center of Engineering Technology for Utilization of Functional Ingredients from Botanicals, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-9762","authenticated-orcid":false,"given":"Xincong","family":"Kang","sequence":"additional","affiliation":[{"name":"College of Horticulture, Hunan Agricultural University, Changsha 410128, China"},{"name":"State Key Laboratory of Subhealth Intervention Technology, Hunan Agricultural University, Changsha 410128, China"},{"name":"Hunan Provincial Engineering Research Center of Medical Nutrition Intervention Technology for Metabolic Diseases, Hunan Agricultural University, Changsha 410128, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","unstructured":"Magliano, D., and Boyko, E.J. 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