High fat diet aggravates intestinal barrier damage in mice with irritable bowel syndrome
10.16352/j.issn.1001-6325.2025.08.1022
- VernacularTitle:高脂饮食加重小鼠肠易激综合征肠屏障损伤
- Author:
Cuijuan ZHAO
1
;
Min AO
;
Wenbo WU
;
Yanhua LI
Author Information
1. 内蒙古医科大学第三临床医学院(内蒙古包钢医院)消化内科,内蒙古包头 014000
- Keywords:
irritable bowel syndrome;
obesity;
peroxisome proliferator-activated receptor-α;
intestinal barrier damage;
inflammatory factors
- From:
Basic & Clinical Medicine
2025;45(8):1022-1027
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects and underlying molecular mechanisms of high fat diet(HFD)on in-testinal barrier damage and inflammatory reaction in mice with irritable bowel syndrome(IBS)induced by sodium dextran sulfate(DSS).Methods C57BL/6 mice were randomly divided into four groups(n=6):Normal group,DSS group(1.5％DSS solution for one week),HFD+DSS group,and HFD+DSS+WY14643 group(intraperitone-ally injected daily with PPARα agonist WY14643 6 mg/kg).The body weight and liver weight of mice were measured.Colon pathology was observed by HE staining.The protein expression of zonula occludens-1(ZO-1)and occludin was detected by immunohistochemistry.The mRNA expression of tumor necrosis factor-α(TNF-α),interleukin-β(IL-1β),and interleukin-17(IL-17)were determined by qRT-PCR.PPARα protein expression was determined by Western blot.Results The body weight and liver weight of mice in the HFD+DSS group were significantly higher than those in the DSS group(P＜0.001).HE staining showed normal colonic tissue structure in Normal group,while other three groups exhibited varying degrees of mucosal damage with a small amount of in-flammatory cell infiltration and epithelial cell shedding.Among these,the HFD+DSS group displayed the most se-vere intestinal mucosal damage and inflammatory infiltration.Compared with the DSS group,the HFD+DSS group showed decreased ZO-1 and Occludin protein expression(P＜0.001),elevated TNF-α,IL-1 β,and IL-17 mRNA levels(all P＜0.001),and downregulated PPARα protein expression(P＜0.01).Compared with the HFD+DSS group,mice in HFD+DSS+WY14643 group showed improvement in intestinal mucosal damage and reduced infiltration of inflammatory cells.The protein expression of ZO-1 and occludin in colon of mice in the HFD+DSS+WY14643 was increased(all P＜0.05),while the expression of TNF-α,IL-1 β,and IL-17 mRNA was downregulated(P＜0.01 or P＜0.05),and the protein expression of PPAR α was upregulated(P＜0.05).Conclusions HFD-induced obesity aggravates intestinal mucosal damage,intestinal barrier destruction and in-flammatory response in IBS mice,and its molecular mechanism is potentially related to downregulation of PPARαexpression in intestinal tissues.
