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TOFA acted more than additively with incretin analogs such as semaglutide and tirzepatide to improve obesity, dyslipidemia, and insulin resistance. Our findings suggest that the coordinated multi-targeting of energy metabolism and lipid homeostasis by TOFA is an effective approach to address multiple associated metabolic diseases.<\/jats:p>","DOI":"10.1126\/sciadv.aed3119","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:58:41Z","timestamp":1787335121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8579-605X","authenticated-orcid":true,"given":"Justin Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences &amp; Toxicology, University of California, Berkeley, CA 94720, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9529-7000","authenticated-orcid":true,"given":"Chi","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences &amp; 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