[Effect of electroacupuncture regulating FXR pathway on glucose and lipid metabolism disorder in obese mice]

To investigate the mechanism of electroacupuncture (EA) regulating glycolipid metabolism and improving obesity by activating farnesoid X receptor (FXR)/takeda G protein-coupled receptor 5 (TGR5)/glucagon-like peptide-1 (GLP-1) and FXR/fibroblast growth factor 15 (FGF15) signaling pathways mediated by intestinal FXR in obese mice induced by high-fat diet.

Fifty SPF male C57BL/6 mice were randomly divided into a blank group (n=8) and a pre-model group (n=42). The obese mice model was established by high-fat diet. Twenty-four obese mice were randomly divided into the model group, the EA group and the sham EA group, with 8 mice in each group. In the EA group, bilateral "Zusanli" (ST36) and "Tianshu" (ST25) were electroacupunctured for 30 min each time. In the sham EA group, ST36 and ST25 were selected to be shallowly pricked to the subcutaneous, and the EA instrument was connected without electricity. Both groups received interventions once every other day, 3 times a week for 4 weeks. The body weight and Lee's index of mice in each group were recorded before and after intervention. The contents of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG) and fasting insulin (FINS) were detected, and the homeostatic model assessment of insulin resistance (HOMA-IR) index was calculated. The morphological changes of intestinal tissue in each group were observed by HE staining. The expression of FXR, TGR5, FGF15 and GLP-1 proteins and mRNAs in intestinal tissue of mice was detected by Western blot and fluorescence quantitative PCR separately.

Compared with the blank group, the body weight, Lee's index, serum TG, TC, LDL-C, FBG, FINS contents and HOMA-IR were increased (P<0.01), the intestinal mucosal tissue was significantly damaged, the mucosal epithelial cells were damaged, shed, and arranged in disorder, there was obvious inflammatory cell infiltration in the stroma, and the expression levels of FXR, TGR5, GLP-1, FGF15 proteins and mRNAs in the ileum tissue were significantly decreased (P<0.01) in the model group. Compared with the model group, the body weight was decreased (P<0.01) in mice of the EA and sham EA groups；the Lee's index, serum TG, TC, LDL-C, FBG, FINS contents and HOMA-IR were decreased (P<0.01), the degree of pathological changes in the ileum tissue was significantly lighter, and the expression levels of FXR, TGR5, GLP-1, FGF15 proteins and mRNAs in the ileum tissue were significantly increased (P<0.01) in mice of the EA group；the expression level of TGR5 mRNA was increased (P<0.01) in the sham EA group. Compared with the EA group, all indicators were reversed (P<0.01) in the sham EA group.

EA can significantly improve the body weight and Lee's index of obese mice, reduce blood lipid content, and improve glucose metabolism and insulin resistance related indicators. The mechanism may be achieved through FXR/TGR5/GLP-1 and FXR/FGF15 signaling pathways.