Mechanism of kaempferol ameliorating hepatic lipid deposition induced by high fat diet based on endoplas-mic reticulum stress-FXR pathway
10.3969/j.issn.1006-5725.2025.16.007
- VernacularTitle:基于内质网应激-FXR途径探讨山柰酚改善高脂饮食诱导的肝脏脂质沉积的机制
- Author:
Shinan ZHOU
1
;
Lu LIANG
;
Wenyan ZHONG
;
Jingjing CHEN
;
Li XIAO
Author Information
1. 三峡大学肿瘤微环境与免疫治疗湖北省重点实验室(湖北 宜昌 443002)
- Publication Type:Journal Article
- Keywords:
kaempferol;
endoplasmic reticulum stress;
farnesoid x receptor;
non-alcoholic steato-hepatitis;
lipid deposition
- From:
The Journal of Practical Medicine
2025;41(16):2481-2488
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the protective effects of Kaempferol(KAE)against hepatic lipid de-position induced by a high-fat diet,as well as the underlying mechanisms.Methods C57BL/6J male mice were fed a high-fat diet for 22 weeks to establish a chronic nonalcoholic steatohepatitis(NASH)model.KAE was admin-istered during the last 8 weeks as an interventional agent to evaluate its effects.Liver lipid deposition was assessed,and the expression levels of endoplasmic reticulum(ER)stress-related proteins,activation of the Farnesoid X Re-ceptor(FXR)signaling pathway,and the expression of lipid synthesis-related genes were analyzed.In vitro,pal-mitic acid(PA)was used to stimulate AML-12 cells to induce lipid accumulation.Additionally,siRNA targeting FXR was transfected into AML-12 cells to investigate the role of the ER stress-FXR signaling pathway in mediating the effects of KAE.Results The intervention of kaempferol inhibited the rapid weight gain induced by a high-fat diet,reduced serum total cholesterol,triglyceride levels,and ALT activity,effectively alleviated large-scale lipid aggregation in the liver,thereby exerting a protective effect against hepatic lipid deposition in NASH.Mechanisti-cally,KAE decreased hepatic ER stress,promoted the expression of FXR and its activation marker SHP,thereby suppressing the expression of FASN and reducing hepatic lipid synthesis.In vitro,KAE treatment significantly re-versed the inhibitory effect of excessive ER stress on FXR activity,as evidenced by the upregulation of FXR activ-ity leading to decreased FASN expression and reduced steatosis in AML-12 cells.Moreover,FXR knockdown mark-edly abolished the protective effects of KAE on lipid deposition in AML-12 cells exposed to PA,by eliminating the promoting effect of KAE on SHP expression and the SHP-mediated suppression of SREBP1c.Conclusions KAE treatment alleviated ER stress,thereby enhancing FXR/SHP signaling and subsequently suppressing lipid synthesis to reduce hepatic lipid accumulation.These findings suggest that KAE holds therapeutic potential for the manage-ment of hepatic steatosis in NASH.
