Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model

Abstract

Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and liver morphological adaption, as well as the changes in bile acids signaling and expression of its target regulatory factors involved in gluconeogenesis, lipogenesis, and fatty acid β oxidation. Twenty adult male T2DM rats induced by high-fat diet and a low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, serum lipid profiles, and bile acids level were assessed to evaluate metabolic changes. Liver sections were stained with hematoxylin-eosin (H&E) and oil red O to assess lipid accumulation. The mRNA and protein expression levels of farnesoid X receptor (FXR), small heterodimer partner (SHP), key regulatory factors of gluconeogenesis, lipogenesis, and fatty acid β oxidation (phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-α (PPAR-α)) were determined through RT-PCR and Western blotting, respectively. RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum TG, FFAs, and increased bile acids levels. The lipid droplets in the liver were significantly decreased after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK, G6Pase, and SREBP-1c and upregulated expression of FXR, SHP, and PPAR-α in the liver. RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The liver exhibited a marked improvement in lipid accumulation after RYGB. The bile acids level, FXR, and its target transcriptional factor SHP expression were elevated. Meanwhile, our study demonstrated that the increased bile acids-FXR signaling, followed by the reduced hepatic gluconeogenesis, lipogenesis, and increased fatty acid β oxidation may contribute to improved metabolic conditions after RYGB.