Mechanism of tight junctional function injury of testicular Sertoli cells induced by high-fat diet based on NF-κB/NLRP3 signaling pathway
- VernacularTitle:基于NF-κB/NLRP3信号通路研究高脂饮食对睾丸支持细胞紧密连接功能损伤的作用及机制
- Author:
Run-min MAO
1
;
Hai-xia ZHAO
;
Hai-li DUAN
;
Zi-hui GAO
;
Ya-nan QU
;
Guo-qing FU
;
Jian-min MAO
;
Jian-ming SUN
;
Chang-cheng ZHANG
Author Information
- Publication Type:Journal Article
- Keywords: high-fat diet; testis; Sertoli cells; tight junction function; inflammation; NF-κB/NLRP3 sig-naling pathway
- From: Chinese Pharmacological Bulletin 2025;41(11):2134-2142
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of high-fat diet on the tight junction function injury of Sertoli cells through the NF-κB/NLRP3 signaling pathway in mice and to explore the underlying mechanism.Methods Male C57BL/6J mice were fed with high-fat or normal diet for five months.The body and gonadal organ weight of mice were measured,and their indices were calculated.The sperm concentration,the sperm viabili-ty,the testicular histomorphology and the expression levels of tight junction proteins ZO-1,Occludin and Claudin-11 were measured.TM4 cells were treated with palmitic acid(PA)for 24 h.Cell viability was detected by CCK-8 method.Then,TM4 cells were di-vided into different groups treated with PA(0,50,100,200 and 300 μmnol·L-1),and the expression lev-els of tight junction proteins ZO-1,Occludin and Clau-din-11 were detected by Western blot.The tight junc-tion permeability of TM4 cells were detected by transepithelial electrical resistance(TEER)and FITC-dextran.The expression levels of mRNA and proteins for the NF-κB/NLRP3 pathway-related factors were de-tected by RT-qPCR and Western blot.Results The results from animal experiments showed that high-fat diet increased body weight and seminal vesicle weight of mice,and decreased testicular index,epididymal in-dex,sperm concentration and sperm motility of mice.High-fat diet also caused testicular tissue structure damage and down-regulated the expression levels of tight junction proteins ZO-1 and Occludin,without af-fecting the expression of Claudin-11.In vitro,PA sig-nificantly down-regulated the expression levels of ZO-1,Occludin and Claudin-11 in TM4 cells,increased the cell permeability,as well as up-regulated the mRNA and protein expression levels of NLRP3/NF-κB signa-ling pathway-related factors in TM4 cells.Conclusions High-fat diet can impair the function of tight junction of testicualr Sertoli cells,and the machanism may be related to the activation of the NF-κB/NLRP3 signaling pathway,resulting in Sertoli cell inflammation in mice.
