Liraglutide improves the inflammatory response in metabolic associated fatty liver disease through stimulator of interferon genes pathway
10.3969/j.issn.1006-6187.2023.12.011
- VernacularTitle:利拉鲁肽通过干扰素基因刺激因子途径改善代谢相关脂肪性肝病炎症反应及机制的研究
- Author:
Qiongqiong FANG
1
;
Linlin JI
;
Hui HUA
;
Chaoyu ZHU
;
Zhen ZHU
;
Li WEI
Author Information
1. 201306 上海海洋大学水产与生命学院生物系
- Keywords:
Liraglutide;
Stimulator of interferon genes;
Inflammatory response;
Metabolic associated fatty liver disease
- From:
Chinese Journal of Diabetes
2023;31(12):938-944
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which Liraglutide improves the inflammatory response in metabolic associated fatty liver disease(MAFLD)by regulating the interferon gene stimulating factor(STING)signaling pathway.Methods 20 male C57BL/6J mice were randomly divided into normal diet group(NC),Liraglutide intervention group(NC+Lir group),high fat diet group(HFD group)and Liraglutide intervention high fat diet group(HFD+Lir group),with 5 in each group.Mouse primary hepato-cytes(MPHs)were divided into normal control(Con)group,Liraglutide intervention group(Con+Lir group),palmitic acid group(PA group)and Liraglutide intervention PA group(PA+Lir group).The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST)in serum and triglyceride(TG)contents in liver were detected.HE and oil red O staining were used to observe the pathological changes in the liver and to calculate the MAFLD activity score(NAS).The mRNA expression levels of STING,IL-1β and TNF-α in tissues and cells were detected by qRT-PCR.The protein expression levels of STING,p-IRF3 and IFN-β were detected by Western blot.Results Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD group were higher than those in NC group(P<0.05 or P<0.01).Body weight,liver tissue weight,serum ALT,AST,liver TG,steatosis,lobular inflammation and balloon-like NAS in HFD+Lir group were lower than those in HFD group(P<0.05 or P<0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in liver of HFD group were higher than those of NC group(P<0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in HFD+ Lir group were lower than those in HFD+ Lir group(P<0.05).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA group were higher than those in Con group(P<0.01).The mRNA expressions of STING,IL-1β,TNF-α and the protein expressions of STING,p-IRF3 and IFN-β in PA+Lir group were lower than those in PA group(P<0.05 or P<0.01).Conclusion Liraglutide ameliorates the high-fat-induced inflammation responses in MAFLD by regulating the STING signaling pathways.