Effect on JNK1 gene silencing on the expression of high-molecular-weight adiponectin in mice with nonalcoholic fatty liver disease

Objective To investigate the effect of JNK1 gene silencing on the expression of high-molecular-weight adiponectin and related pathway molecules in adipose tissue of mice with nonalcoholic fatty liver disease(NAFLD). Methods A total of 20 C57 BL/6 mice were randomly divided into normal group,model control group,NAFLD group treated with shRNA-JNK1 lentivirus(JNK1 + NAF group),and NAFLD group treated with unrelated-sequence shRNA lentivirus(unrelated sequence + NAF group),with 5 mice in each group. Normal diet and high-fat diet were given for 3 months,and a mouse model of NAFLD was successfully established. The mice with NAFLD were given tail vein injection of shRNA-JNK1 lentivirus with the optimal interfering effect and unrelated-sequence shRNA lentivirus. After 5 days of feeding based on diet and lentivirus injection,HE staining was used to observe the pathological changes of liver tissue. ELISA was used to measure the serum level of high-molecular-weight adiponectin. Western blot was used to measure the expression of AMP-activated protein kinase(AMPK),phosphorylated AMPK(p-AMPK),high-molecular-weight adiponectin,and disulfide-bond-A oxidoreductase-like protein(DsbA-L) in epididymal fat pad. A one-way analysis of variance was used for comparison of continuous data between groups,and the least significant difference t-test was used for further comparison between two groups. Results HE staining showed that compared with the model control group,the JNK1 + NAF group had significant reductions in lipid droplet vacuoles,edema,and inflammation. The JNK1 + NAF group had a significantly lower liver steatosis score than the model control group and the unrelated sequence + NAF group(2. 267 ± 0. 704 vs 3. 800 ± 0. 414/3. 667 ± 0. 617,both P < 0. 05). ELISA showed that the JNK1 + NAF group had a significantly higher serum level of high-molecular-weight adiponectin than the model control group(294. 71 ± 102. 30 ng/ml vs 124. 06 ± 70. 58 ng/ml,P<0. 001). Western Blot showed that the JNK1 + NAF group had significantly higher expression levels of AMPK,p-AMPK,DsbA-L,andhigh-molecular-weight adiponectin than the model control group and the unrelated sequence + NAF group(all P < 0. 05). Conclusion JNK1 gene silencing can promote the expression of Dsb A-L and high-molecular-weight adiponectin in NAFLD mice,activate the AMPK pathway to regulate adiponectin multimerization,and thus improve fat deposition in NAFLD.