Roux-en-Y Gastric Bypass Improves Hepatic Glucose Metabolism Involving Down-Regulation of Protein Tyrosine Phosphatase 1B in Obese Rats

Abstract

Objective: 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. Methods: 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. Results: 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). Conclusion: 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.

Gastric Bypass Surgery Regulates Glucose Homeostasis Through the Hypothalamus

“…Eight weeks after RYGB, hepatic glucose metabolism was improved in obese rats, and PTP1B expression was down-regulated. PTP1B expression was correlated with plasma GLP-1 levels [49]. At the same time, in another 8-week study of obese rats, RYGB also effectively reduced the expression of PTP1B in the hypothalamus of obese rats and enhanced the activity of leptin signalling [50].…”

Does bisphenol-A affect alteration of gut microbiome after bariatric/metabolic surgery?: a comparative metagenomic analysis in a long-term high-fat diet induced-obesity rat model

“…Meanwhile, the subanalysis between the SG and RYGB procedures showed that blood glucose levels remained similar in both groups ( Fig. 3F ); this implies that bariatric surgery was beneficial in improving glucose tolerance, increasing insulin sensitivity, or hepatic glycogen deposition, regardless of BPA exposure [ 27 ].…”

Effects of sleeve gastrectomy on bone mass, microstructure of femurs and bone metabolism associated serum factors in obese rats

“…We speculated SG could decrease leptin production in obese rats, and reduced leptin might play a part in the bone loss after SG. The hepatic expression of PTP1B was significantly decreased in obese rats after Roux-en-Y gastric bypass [ 29 ]. However, the impact of SG surgery on PTP1B and the relationship between PTP1B and BMD have not been illustrated yet.…”

“…Knocking out of PTP1B in mice could contribute to improved insulin sensitivity and attenuated hyperglycemia in obese mice [ 28 ]. Song et al [ 29 ] indicated that Roux-en-Y gastric bypass could down-regulate the expression level of PTP1B in liver and improve hepatic glucose metabolism in obese rats. Katherine Zee et al [ 30 ] found that the protein tyrosine phosphatases (PTPs) had relevance to the development and maintenance of the skeleton.…”