Mu Song, Liu Jiayu, Guo Wei, Zhang Shuping, Xiao Xiaoqiu, Wang Zhihong, Zhang Jun
Department of General Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Obes Facts. 2017;10(3):191-206. doi: 10.1159/000470912. Epub 2017 Jun 1.
This study was initiated to investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on hepatic glucose metabolism and hepatic expression of protein tyrosine phosphatase 1B (PTP1B) in obese rats.
Body weight, glucose, intraperitoneal glucose, insulin, and pyruvate tolerance tests were performed pre- and postoperatively, and plasma lipid, insulin and glucagon-like peptide 1 (GLP-1) were measured. The mRNA levels of G6Pase, Pepck, Gsk-3β and Gys-2, and the expression levels of PTP1B mRNA, protein, and other components of the insulin signaling pathway were measured by using RT-PCR and western blotting. The intracellular localization of PTP1B and hepatic glycogen deposition was also observed.
RYGB surgery-treated rats showed persistent weight loss, significantly improved glucose tolerance, pyruvate tolerance, and dyslipidemia, as well as increased insulin sensitivity, hepatic glycogen deposition and increased plasma GLP-1 in obese rats. RT-PCR analyses showed Pepck, G6Pase, and Gsk-3β mRNA to be significantly decreased, and Gys-2 mRNA to be significantly increased in liver tissue in the RYGB group (p < 0.05 vs. high-fat diet (HFD) or HFD + sham group); in addition, the expression of PTP1B were significantly decreased and insulin signaling were improved in the RYGB group (p < 0.05 vs. HFD or HFD + sham group).
RYGB can improve hepatic glucose metabolism and down-regulate PTP1B in obese rats. An increased circulating GLP-1 concentration may be correlated with the effects following RYGB in obese rats.
本研究旨在探讨Roux-en-Y胃旁路术（RYGB）对肥胖大鼠肝脏葡萄糖代谢及蛋白酪氨酸磷酸酶1B（PTP1B）肝脏表达的影响。
在术前和术后进行体重、葡萄糖、腹腔内葡萄糖、胰岛素及丙酮酸耐量试验，并测定血浆脂质、胰岛素和胰高血糖素样肽1（GLP-1）。采用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法测定葡萄糖-6-磷酸酶（G6Pase）、磷酸烯醇式丙酮酸羧激酶（Pepck）、糖原合成酶激酶-3β（Gsk-3β）和糖原合成酶（Gys-2）的mRNA水平，以及PTP1B mRNA、蛋白质和胰岛素信号通路其他成分的表达水平。同时观察PTP1B的细胞内定位及肝脏糖原沉积情况。
接受RYGB手术的大鼠体重持续减轻，葡萄糖耐量、丙酮酸耐量和血脂异常显著改善，胰岛素敏感性增加，肝脏糖原沉积增加，肥胖大鼠血浆GLP-1升高。RT-PCR分析显示，RYGB组肝脏组织中Pepck、G6Pase和Gsk-3β mRNA显著降低，Gys-2 mRNA显著升高（与高脂饮食（HFD）或HFD+假手术组相比，p<0.05）；此外，RYGB组PTP1B表达显著降低，胰岛素信号通路得到改善（与HFD或HFD+假手术组相比，p<0.05）。
RYGB可改善肥胖大鼠肝脏葡萄糖代谢并下调PTP1B。循环中GLP-1浓度升高可能与肥胖大鼠RYGB术后的效应相关。
