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This study investigated how kaempferol regulates adipogenesis in 3T3-L1 preadipocytes and exerts antiobesity effects in high-fat diet (HFD)-induced obese mice. Kaempferol inhibited preadipocyte differentiation at the early mitotic clonal expansion (MCE) stage by S-phase (18\u202fh) and G2\/M-phase (24\u202fh) cell cycle arrest. Mechanistically, this action was mediated through inhibition of the PI3K\/AKT\/GSK3\u03b2 pathway. Application of the AKT activator SC79 confirmed that kaempferol suppresses AKT phosphorylation to inhibit terminal adipogenesis. In vivo, kaempferol significantly alleviated HFD-induced body weight gain, adiposity, dyslipidemia, and insulin resistance. Transcriptomic and histological analyses revealed that kaempferol reversed obesity-associated upregulation of cell cycle and metabolic pathways in white adipose tissue and alleviated adipose tissue fibrosis. These findings underscore the potential of kaempferol as a promising functional food ingredient for preventing obesity and related metabolic diseases.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c00834","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:02:28Z","timestamp":1786366948000},"page":"25183-25201","source":"Crossref","is-referenced-by-count":0,"title":["Kaempferol Counteracts\nObesity and Impairs Adipogenesis\nby Suppressing PI3K\/AKT\/GSK3\u03b2-Mediated Mitotic Clonal Expansion\nand Attenuating Adipose Tissue Fibrosis"],"prefix":"10.1021","volume":"74","author":[{"given":"Xia","family":"Du","sequence":"first","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. China, 311400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaling","family":"Tang","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. China, 311400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilu","family":"Shou","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. China, 311400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsa","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. China, 311400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Peng","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. China, 311400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University , , ,","place":["Hangzhou, P. R. 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