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This study aimed to investigate the anti-obesity effects of denatonium benzoate (DB) and elucidate its underlying mechanisms. Methods: In order to study the anti-obesity effects of DB and its mechanisms, we used in vivo and in vitro obesity models to study whether DB has anti-obesity effects by participating in fat browning. We investigated the role of DB in high-fat diet (HFD)-induced obese C57BL\/6J mice using 36 male animals (8 weeks old, 25 \u00b1 2 g), and evaluated the expression of the adipogenic marker genes Fatty acid-binding protein 4 (Fabp4) and Peroxisome Proliferator-Activated Receptor gamma (PPAR-\u03b3); the thermogenic genes uncoupling protein 1 (Ucp1), Transcription Factor A, Mitochondrial (TFAM), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-Alpha (Pgc1\u03b1), and Adrenergic receptor beta 3 (Adrb3); as well as the adipose browning marker genes Deiodinase, Iodothyronine, Type II (Dio2), PR domain containing 16 (PRDM16), and Peroxisome Proliferator-Activated Receptor alpha (PPAR-\u03b1) in 3T3-L1 cells and primary adipocytes with DB treatment. Conclusions: These results indicate that the anti-obesity effects of DB may be related to the browning of white fat, providing a novel potential candidate for anti-obesity drug development.<\/jats:p>","DOI":"10.3390\/metabo16040242","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:09:54Z","timestamp":1775138994000},"page":"242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Denatonium Benzoate, the Most Bitter Compound, Reduces Weight by Promoting Adipocyte Browning"],"prefix":"10.3390","volume":"16","author":[{"given":"Yiqin","family":"Niu","sequence":"first","affiliation":[{"name":"School of Pharmacy, Binzhou Medical University, Yantai 264003, China"},{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Shao","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Teng","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ce","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2314-4800","authenticated-orcid":false,"given":"Xin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Binzhou Medical University, Yantai 264003, China"},{"name":"Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai 264117, China"},{"name":"State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimeng","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/S0140-6736(22)02403-5","article-title":"Contemporary medical, device, and surgical therapies for obesity in adults","volume":"401","author":"Perdomo","year":"2023","journal-title":"Lancet"},{"key":"ref_2","unstructured":"World Health Organization (2024). 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