Kaempferol Counteracts Obesity and Impairs Adipogenesis by Suppressing PI3K/AKT/GSK3β-Mediated Mitotic Clonal Expansion and Attenuating Adipose Tissue Fibrosis
Xia Du, Yaling Tang, Yilu Shou, Jingsa Zhang, He Peng, Jiajun Chen, Yan Li, Die Wu, Chunsheng Xu, Menghao Du, Fengling Zhang, Xingya WangAbstract
Kaempferol, a widely present dietary flavonoid in numerous fruits and vegetables, possesses antiobesity potential with unclearly defined mechanisms. 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 h) and G2/M-phase (24 h) cell cycle arrest. Mechanistically, this action was mediated through inhibition of the PI3K/AKT/GSK3β 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.