Study of the effect of liraglutide on the correlation between NLRP3 inflammasome and non-alcoholic fatty liver disease

Abstract

Objective: To observe the effect of liraglutide on the correlation between nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) infl ammasome and nonalcoholic fatty liver disease (NAFLD). Methods: Thirty-nine NAFLD cases (group N) and thirty-nine healthy subjects (group C) were selected from the physical examination center, and their general data were collected to determine the serum levels of NLRP3, IL-1β, and IL-18. The differences and correlations were analyzed between the two sets of indicators. Thirty male SD rats were randomly divided into normal (NC, n=10) and high-fat diet group (HF, n=20). The normal group were fed with normal diet and high-fat diet group were fed with high-fat diet. After 12 weeks of feeding, HF group was randomly divided into HF group (n=10) and liraglutide group (100L, n=10), and were given 0.5 ml/kg sterile isotonic saline and 100 g/kg liraglutide subcutaneously twice a day, respectively. Four weeks later, serum biochemical indicators, liver NLRP3 infl ammasome protein expression, and infl ammatory cytokine conditions were detected in each group. Statistical analysis was performed using t test, oneway analysis of variance (ANOVA) or χ2 test. Results: There were no statistically signifi cant differences between N and C group in terms of age, gender, diastolic blood pressure, glycosylated hemoglobin, mean platelet volume, erythrocyte distribution width, serum low-density lipoprotein cholesterol (HDL-Ch), total cholesterol, and total bileacid. Compared with group C, group N had elevated systolic blood pressure, body mass index (BMI), fasting blood glucose, blood creatinine, alkaline phosphatase (ALP), NLRP3, interleukin (IL)-1β, IL-18, TG, blood uric acid, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and white blood cell counts, while HDL-Ch and total bilirubin were depleted than group C, and the difference was statistically significant (P< 0.05). NLRP3 was positively correlated with systolic blood pressure, BMI, fasting blood glucose, serum creatinine, IL-1β, IL-18, triglycerides, serum uric acid, GGT, ALT, AST, but negatively correlated with total bilirubin and HDL-Ch, and the difference was statistically signifi cant. Compared with NC group, HF group had significantly increased body mass, liver mass, serum biochemical indicators (triglycerides, AST, ALT), liver NLRP3 inflammasome protein expression, and inflammatory cytokines. After treatment with liraglutide, 100L group indicators were signifi cantly decreased when compared to HF group. Conclusion: Compared with healthy subjects, the infl ammation-related indicators, body mass, blood lipids and liver function-related indicators are signifi cantly changed in patients with NAFLD, which is also consistent with the results of rat model study. Liraglutide treatment had improved NAFLD to certain extent in NAFLD rats, so NLRP3 regulation may be one of the mechanisms to improve liver inflammation and steatosis.