Cholecystectomy with jejunoileal bypass ameliorates diabetic metabolism in mice with type 2 diabetes through modulation of FXR and TGR5 signaling.

OBJECTIVES

Our aim was to investigate the improvement in glucose and lipid profiles and the mechanism involving bile acid receptors FXR and TGR5 following cholecystectomy with jejunoileal bypass(CJB) in mice with type 2 diabetes mellitus (T2DM).

METHODS

Twenty male mice with T2DM were randomly assigned to CJB and sham groups. We analyzed fasting blood glucose (FBG), insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and total bile acids (TBA) levels. Expression levels of the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5) in liver, muscle, and adipose tissue were assessed post-sacrifice.

RESULTS

Despite pair-feeding, the CJB group exhibited lower body weights than the sham group at 24 weeks post-surgery (P = 0.004). The levels of FBG (P < 0.001) and insulin (P = 0.013) in the CJB group significantly decreased compared to the baseline. The intraperitoneal glucose and insulin tolerance tests demonstrated improved glucose tolerance (P = 0.004) and insulin sensitivity (P = 0.001). GLP-1 levels significantly increased (P = 0.002). The levels of TC (P < 0.001) and LDL-C (P < 0.001) were decreased, while the levels of TG (P = 0.003), HDL-C (P < 0.001), and FFA (P < 0.001) were increased at the 24th postoperative week. Furthermore, TBA concentrations were higher in the CJB group than in the control group (P < 0.001). The expression of FXR in the liver (P = 0.034), muscle (P = 0.003) and adipose tissue (P = 0.045) and that of TGR5 in the liver (P = 0.024), muscle (P = 0.026) and adipose tissue (P = 0.004) were upregulated after surgery.

CONCLUSIONS

In mice with T2DM, cholecystectomy with jejunoileal bypass modulates BA-FXR/TGR5 signaling and is associated with metabolic improvement.