MAFB mediates the therapeutic effect of sleeve gastrectomy for obesediabetes mellitus by activation of FXRexpression

摘要

Farnesoid X receptor (FXR) and related pathways are involved in the therapeutic effect of sleeve gastrectomy for overweight or obese patients with diabetes mellitus. This study aimed to investigate the mechanism of FXR expression regulation during the surgical treatment of obese diabetes mellitus by sleeve gastrectomy. Diabetic rats were established by combined streptozotocin and high-fat diet induction. Data collection included body weight, chemical indexes of glucose and lipid metabolism, liver function, and the expression levels of musculoaponeurotic fibrosarcoma oncogene family B (MAFB), FXR, and related genes induced by sleeve gastrectomy. Chang liver cells overexpressing MAFB gene were established to confirm the expression of related genes. The binding and activation of FXR gene by MAFB were tested by Chip and luciferase reporter gene assays. Vertical sleeve gastrectomy induced significant weight loss and decreased blood glucose and lipids in diabetic rat livers, as well as decreased lipid deposition and recovered lipid function. The expression of MAFB, FXR, and FXR-regulated genes in diabetic rat livers were also restored by sleeve gastrectomy. Overexpression of MAFB in Chang liver cells led toFXR gene expression activation and the alteration ofmultiple FXR-regulated genes. Chip assay showed that MAFB coulddirectly bind with FXR promoter, and the activation of FXR expression wasconfirmed by luciferase reporter gene analysis. The therapeutic effect of sleevegastrectomy for overweight or obese patients with diabetes mellitus was mediatedby activation of FXR expression through the binding of MAFBtranscription factor.