To explore the effects of gastric sleeve resection (SG) on adipokine neuregulin 4(Nrg4) in the peripheral circulation of obese mice, and to explore the role and mechanism of Nrg4 in the improvement of hepatic steatosis by SG.

Sham operation (n=3 mice), SG (n=3 mice) and NRG4-overexpressed adeno-associated virus (n=3 mice) were performed on obese model mice, respectively. Differences in body weight, lipid metabolism indexes and liver fat infiltration were observed, and differences in Nrg4 concentration in peripheral blood of mice after operation were detected, and differences in expression of key enzymes in fatty acid synthesis pathway were detected. Mouse hepatocytes with Nrg4 overexpression were constructed to verify the effect of Nrg4 on the expression of key enzymes in fatty acid synthesis pathway, and the differences in fat deposition in hepatocytes with different Nrg4 expression levels. GraphPad Prism 9 software was used for data analysis. Measurement data of each group were expressed as (), and ANOVA was used for comparison between groups. P<0.05 was considered statistically significant.

Obese mice that received SG or Nrg4 overexpression adenovirus-related virus intervention significantly decreased body weight (P<0.0001), peripheral blood total cholesterol (TC) and triglyceride (TG) levels were significantly decreased (TC: P<0.01, TG: P<0.05), liver fat infiltration was alleviated, and peripheral blood Nrg4 concentration was increased (SG: P<0.0001, Nrg4 overexpression: P<0.001), liver fatty acid synthase (Fasn) and acetyl-CoA carboxylase 1(Acc1) expression decreased (Fasn: P<0.0001, Acc1: P<0.05); The expression of Fasn and Acc1 in hepatocytes with Nrg4 overexpression decreased, and the lipid deposition was less than that in sham operation group.

SG can increase Nrg4 concentration in peripheral circulation and decrease liver fatty acid synthesis mediated by Nrg4, thus ameliorating liver lipid metabolism disorder.