Effect of silencing IGFBP7 expression on nonalcoholic fatty liver disease
10.3969/j.issn.1672-2159.2024.02.010
- VernacularTitle:沉默IGFBP7的表达对非酒精性脂肪肝的影响
- Author:
Hua YAN
1
;
Dan ZHANG
;
Jian NIE
;
Min LI
Author Information
1. 710068 陕西省人民医院老年病院
- Keywords:
NAFLD;
High fat diet;
1GFBP7;
Steatosis;
Lipid metabolism;
shRNA
- From:
Modern Interventional Diagnosis and Treatment in Gastroenterology
2024;29(2):170-175
- CountryChina
- Language:Chinese
-
Abstract:
Objective This study aims to explore the role of Insulin-like growth factor binding protein(IGFBP)7in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).Methods A mouse model of NAFLD was established by feeding a high-fat diet and IGFBP7 was knocked out by injecting adeno-associated virus(AAV)-mediated short hairpin(sh)-IGFBP7 into the liver.The mice were randomly divided into 4 groups(n=6 per group):normal diet group(ND),high fat diet group(HFD),HFD empty carrier injection group(HFD/AAV-null),and HFD AAV-sh-IGFBP7 injection group(HFD/AAV-sh-IGFBP7).ND group was given normal diet for 12 weeks,HFD group,HFD/AAV-null group and HFD/AAV-sh-IGFBP7 group were given high fat diet for 4 weeks.HFD/AAV-sh-IGFBP7 group and HFD/AAV-null group were injected with 2 × 1011 genome copies of AAV-sh-IGFBP7 or AAV-null group,respectively,and then continued to be fed for 8 weeks.Body weight,liver wet weight and liver index of mice in each group were determined.Serum triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),free fatty acid(FFA),glycerol and liver TG of mice in each group were detected by biochemical analyzer.Real-time quantitative PCR and Western blot were used to detect IGFBP7 mRNA in each group.Protein expression levels and mRNA expression levels of sterol regulatory element binding protein 1c(SREBP-1c),fatty acid synthase(FASN),acetyl-CoA carboxylase1(ACC1)and stearoyl-CoA desaturase 1(SCD1)related to lipogenesis.Results Compared with ND group,body weight,liver wet weight,liver index and serum ALT,AST,FFA,TG,TC,glycerol and liver TG levels in HFD group were significantly increased,and the differences were statistically significant(P＜0.05),while body weight,liver wet weight,liver index and serum ALT,AST,and serum TG levels in HFD/AAV-sh-IGFBP7 group were significantly increased(P＜0.05).FFA,TG,TC,glycerol and liver TG levels increased less than those of HFD/AAV-null group,and the differences were statistically significant(P＜0.05).Compared with ND group,the expression levels of IGFBP7mRNA and protein in liver of mice in HFD group were increased,and the difference was statistically significant(P＜0.01).Compared with HFD/AAV-null group,the expression level of IGFBP7 protein in liver of HFD/AAV-sh-IGFBP7 group was significantly decreased,and the difference was statistically significant(P＜0.01).Compared with ND group,mRNA expression levels of SREBP-1c,FASN,ACC1 and SCD1 in liver tissues of mice in HFD group were significantly increased,with statistical significance(P＜0.01).Compared with HFD/AAV-null group,mRNA expression levels of SREBP-1c,FASN,ACC1 and SCD1 in HFD/AAV-sh-IGFBP7 group were decreased,and the difference was statistically significant(P＜0.01).Conclusion IGFBP7 is involved in hepatic steatosis during the development of NAFLD.Down-regulation of IGFBP7 can reduce the accumulation of lipid in the liver and has a protective effect on the pathogenesis of NAFLD,which may be a new drug for the treatment of NAFLD.
