Roux-en-Y Gastric Bypass Surgery Alleviates Leptin Resistance Associated With Downregulation Of Protein Tyrosine Phosphatases 1B In Obese Rats

Objective: It has been systematically reported that,Roux-en-Y gastric bypass surgery is the most effective therapeutic method for obesity,but the exact mechanisms have not been fully known.Since the leptin is important for metabolism,the aim of the present study was to investigate the impact of RYGB surgery on protein tyrosine phosphatase 1B(PTP1B)expression levels and leptin activity in the hypothalamus of obese rats.Methods: Male SD rats were induced by high fat food to create obese model.After 12 weeks,the rats whose body weights were 20% greater than the normal control group were selected as obese models.Obese rats were randomly assigned into three groups: RYGB(n = 12),sham-operation(SO,n = 8),and an obese control group(Obese,n = 8);And an additional normal control group(Lean)(n = 10).Food efficiency was measured at the 8th week post-operation.At the 12 th week post-operation,the body fat percentage was examined by DEXA.Then animals were sacrificed for collecting plasma and hypothalamus.Plasma leptin levels were detected by ELISA,and hypothalamic PTP1 B levels and leptin signaling activity were examined at the genetic and protein levels.The body weights were recorded weekly.Results: The obese model and surgical model were created successfully.The plasma leptin levels were much higher in Obese rats compared with the Lean rats.Meanwhile,the level of leptin in RYGB rats was lower than that of SO rats,but similar to that of Lean rats.The food efficiency was typically lower in RYGB rats than that of SO and Obese rats.The p-STAT3 protein levels were much higher in RYGB group compared with the SO and Obese groups.Furthermore,the leptin Receptor(Lep-R)expression was higher in RYGB group than SO and Obese groups.Proopiomelanocortin(POMC)was significantly higher in RYGB group than SO and Obese groups.In contrast,the Neuropeptide Y(NPY)levels were lower in RYGB group than SO and Obese groups.And the PTP1 B at gene and protein expression levels were lower in RYGB group than in SO and Obese groups.Conclusion: RYGB surgery could reduce body weight efficiently.This might be resulted from down regulating hypothalamic PTP1 B level and then improving Leptin signaling pathway activity.