{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T07:34:53Z","timestamp":1785483293011,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104479"],"award-info":[{"award-number":["82104479"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803897"],"award-info":[{"award-number":["81803897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine","award":["LSLSKL20240128"],"award-info":[{"award-number":["LSLSKL20240128"]}]},{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine","award":["LSLSKL20240130"],"award-info":[{"award-number":["LSLSKL20240130"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Rosiglitazone (RSG), a potent PPAR\u03b3 agonist for type 2 diabetes mellitus (T2DM), induces adverse adipogenic effects that limit clinical use. We investigated whether emodin (1,3,8-trihydroxy-6-methylanthraquinone, EMO), a natural anthraquinone, mitigates RSG-induced complications while enhancing its insulin-sensitizing benefits in severe obesity. Methods: Male ob\/ob mice with established obesity and diabetes were treated for 4 weeks with RSG (10 mg kg\u22121 day\u22121), EMO (200 or 400 mg kg\u22121 day\u22121) or their combination. Metabolic profiling, organ function, and adipose histology were analyzed. RNA sequencing and mechanistic studies (Western blot, RT-qPCR, luciferase assays) in inguinal subcutaneous adipose tissue (iSAT), epididymal white adipose tissue (eWAT), and 3T3-L1 adipocytes were used to define EMO\u2019s actions. Results: EMO co-treatment dose-dependently reduced RSG-induced weight gain, visceral adiposity (iSAT and eWAT mass, p &lt; 0.05), and ectopic lipid deposition while ameliorating hepatorenal dysfunction. EMO synergistically enhanced RSG\u2019s glucose-lowering effects. Mechanistically, EMO suppressed sterol regulatory element-binding protein 1 (SREBP1)-mediated lipogenesis (Srebp1, Acc, Fasn, Scd1; p &lt; 0.05) and enhanced PPAR\u03b3-peroxisome proliferator-activated receptor gamma coactivator-1\u03b1 (PGC-1\u03b1)-driven thermogenesis via enhanced PPAR\u03b3 transactivation and nuclear translocation. Thermogenic genes (Ucp1, Ppargc1a, Cidea; p &lt; 0.05) were upregulated, with maximal uncoupling protein 1 (UCP1) induction in iSAT at 400 mg\/kg EMO. Conclusions: EMO selectively enhances RSG\u2019s glycemic benefits while attenuating its adipogenic effects in severe obesity by dual PPAR\u03b3 modulation-inhibiting adipogenic pathways while amplifying thermogenesis. This strategy mitigates RSG\u2019s adverse effects while improving insulin sensitivity, supporting the potential of EMO as a PPAR\u03b3 adjunct therapy.<\/jats:p>","DOI":"10.3390\/ph18121810","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"1810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Emodin Enhances Rosiglitazone\u2019s Therapeutic Profile by Dual Modulation of SREBP1-Mediated Adipogenesis and PPAR\u03b3-Driven Thermogenesis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3602-3429","authenticated-orcid":false,"given":"Meng","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"},{"name":"School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Rong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"CAS Engineering Laboratory for Nutrition, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7050-8940","authenticated-orcid":false,"given":"Yun-Hong","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"},{"name":"School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-An","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0316-7880","authenticated-orcid":false,"given":"Yan-Qi","family":"Dang","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Digestive Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China"},{"name":"State Key Laboratory of Integration and Innovation of Classical Formula and Modern Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. 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