Gastric bypass surgery therapy for obese type 2 diabetes mellitus by reducing methylation of PPARGC1A gene promoter

Guang-Wei Wang, Zhong-Qi Mao#

Department of Mini-mally Invasive Surgery, the First Affiliated  Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China

Objective: To investigate the effect of gastric bypass surgery on the methylation level of PPARGC1A gene promoter in obese type 2 diabetes. 

Methods: This subject collected laparoscopic gastric bypass surgery performed in the First Affiliated Hospital of Soochow University from February 2012. 33 clinical cases of obese type 2 diabetes (BMI>28kg/m2) were followed up for the third and sixth months after surgery. The values of body weight, height, fasting blood glucose, glycosylated hemoglobin, triglyceride and total cholesterol were recorded .We constructed a rat model of obese type 2 diabetes and performed RYGB on them. Their islet cells were cultured after dissecting pancreas. The promoter methylation level of PPARGC1A gene was detected by Bisulfite sequencing PCR (BSP). To certify whether the correlation between the expression of PPARGC1A mRNA and the amount of insulin secretion, transfection of PPARGC1A-siRNA was used to test rats’ islet cells by high glucose stimulation.

Results: All patients were discharged smoothly after surgery. The BMI, fasting blood glucose, HbAlc and TG levels in the patients after surgery were significantly lower than those before surgery, while the TC values did not change much. The methylation level of PPARGC1A gene promoter in islet cells of obese type 2 diabetic rats increased, and the lower methylation level could be restored after gastric bypass surgery. The promoter methylation of PPARGC1A gene was negatively correlated with its relative expression level of mRNA, while the relative expression of PPARGC1A mRNA was positively correlated with the insulin secretion stimulated by high glucose (16.7mmol/L glucose).

Conclusions: Laparoscopic Roux-en-Y gastric bypass is a relatively safe and effective weight loss surgery. This surgery obesity type 2 diabetes mellitus may improve the expression of ppagc1a mRNA and insulin secretion of islet cells stimulated by high glucose (16.7ml / L glucose) through the reduction of methylation in the promoter region of PPARGC1A gene, so as to achieve the purpose of treatment in the obese ty 2diabetes.