Effects of Sleeve Gastrectomy on Serum 12α-Hydroxylated Bile Acids in a Diabetic Rat Model.

Abstract

Diabetes mellitus is a prevalent disease that endangers human health. Bariatric surgery can effectively relieve insulin resistance with elevated serum bile acids (BAs). 12α-Hydroxylated BAs were previously reported to be associated with insulin resistance. The aim of this study was to analyze changes in 12α-hydroxylated BA composition and possible associated mechanisms in diabetic rats following sleeve gastrectomy (SG). SG and sham operations were performed in diabetic rats induced by high-fat diet feeding and streptozotocin. Body weight, food intake, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum BAs were analyzed at corresponding time points. Cholesterol 12α-hydroxylase (CYP8B1) and transcription factor V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog G (MAFG) expression levels were assessed by RT-PCR and western blotting. Compared with the SHAM group, the SG group displayed significant weight loss from 6weeks postoperatively, accompanied by decreased food intake from 4weeks after the operation. At 2 and 12weeks postoperatively, the areas under the curve of OGTT and ITT were significantly decreased in the SG group. At 12weeks post-operation, the SG group displayed elevated serum BAs, but the percentage of 12α-hydroxylated BAs was reduced. Furthermore, SG rats exhibited higher MAFG and lower CYP8B1 protein and mRNA levels in the liver (P<0.05). The percentage of 12α-hydroxylated bile acids was reduced after SG, which was relevant with the inhibition of CYP8B1 and overexpression of MAFG. These outcomes may play an important role in the improvement of insulin sensitivity following SG.