Wang Minggang, Wu Qunzheng, Xie Haibin, Shao Yi, Zhong Mingwei, Zhang Xiang, Liu Shaozhuang, He Xiao, Hu Sanyuan, Zhang Guangyong
Department of Hernia and Abdominal Wall Surgery, Beijing Chao-Yang Hospital, Capital Medical University, 100043, Beijing, People's Republic of China.
Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
Obes Surg. 2017 Nov;27(11):2912-2918. doi: 10.1007/s11695-017-2714-6.
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 6 weeks postoperatively, accompanied by decreased food intake from 4 weeks after the operation. At 2 and 12 weeks postoperatively, the areas under the curve of OGTT and ITT were significantly decreased in the SG group. At 12 weeks 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.
糖尿病是一种危害人类健康的常见疾病。减重手术可通过升高血清胆汁酸（BAs）有效缓解胰岛素抵抗。先前有报道称12α-羟基化胆汁酸与胰岛素抵抗有关。本研究旨在分析糖尿病大鼠行袖状胃切除术（SG）后12α-羟基化胆汁酸组成的变化及可能的相关机制。
对高脂饮食喂养联合链脲佐菌素诱导的糖尿病大鼠进行SG手术和假手术。在相应时间点分析体重、食物摄入量、口服葡萄糖耐量试验（OGTT）、胰岛素耐量试验（ITT）和血清胆汁酸。通过逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法评估胆固醇12α-羟化酶（CYP8B1）和转录因子V-Maf禽肌动蛋白神经纤维肉瘤致癌基因同源物G（MAFG）的表达水平。
与假手术组相比，SG组术后6周体重显著减轻，术后4周食物摄入量减少。术后2周和12周，SG组OGTT和ITT曲线下面积显著降低。术后12周，SG组血清胆汁酸升高，但12α-羟基化胆汁酸的百分比降低。此外，SG大鼠肝脏中MAFG蛋白和mRNA水平较高，CYP8B1蛋白和mRNA水平较低（P<0.05）。
SG术后12α-羟基化胆汁酸百分比降低，这与CYP8B1的抑制和MAFG的过表达有关。这些结果可能在SG术后胰岛素敏感性改善中起重要作用。
