Abstract: Objective:To investigate the effects of Roux-en-Y gastric bypass(RYGB) surgery on the inflammation and lipid accumulation of brain tissue in obese rats induced by high fat diet.Methods:Thirty Wistar rats were randomly divided into the normal diet group(ND group),high-fat diet group(HFD group) and high-fat diet plus RYGB group(HFD plus RYGB group)(10 rats each group).The ND group was treated with the normal diet,and the HFD group and HFD plus RYGB group were treated with high-fat diet.After 16 weeks,the ND group and HFD group were treated with sham operation,and the HFD plus RYGB group was treated with RYGB.After operation,the ND group was continuously treated with the normal diet,and the HFD group and HFD plus RYGB group were continuously treated with high-fat diet.Rats were sacrificed after 4 weeks of operation.The levels of serum triglyceride(TG),total cholesterol(TC) and free fatty acid(FFA) in three groups were detected using ELISA.The levels of diacylglycerol(DAG),FFA,TNF-α,IL-1 and IL-6 in brain tissue of three groups were measured using ELISA.The expressions of Iba-1 and glial fibrillary acidic protein(GFAP) in hypothalamus brain tissue were observed by immunohistochemistry.The neuronal morphology in hypothalamus brain was observed using electron microscope.Results:The levels of serum TG,TC and FFA in HFD group were higher than those in ND group and HFD plus RYGB group(P<0.05 to P<0.01).The level of FFA in HFD plus RYGB group was significantly higher than that in ND group(P<0.01),and the differences of the levels of TG and TC between HFD plus RYGB group and HFD group were not statistically significant(P>0.05).The levels of DAG and FFA in brain tissue of HFD group were significantly higher than those in HFD plus RYGB group and ND group(P<0.01),and the levels of DAG and FFA in brain tissue of HFD plus RYGB group were significantly higher than those in ND group(P<0.01).The levels of TNF-α,IL-1 and IL-6 in brain tissue of ND group and HFD plus RYGB group were significantly lower than those in HFD group(P<0.01).The level of TNF-α in brain tissue of HFD plus RYGB group was significantly higher than that in ND group(P<0.01),but the differences of the levels of IL-1 and IL-6 between HFD plus RYGB group and ND group were not statistically significant(P>0.05).The immunohistochemistry results showed that the number of the Iba-1 and GFAP positive cells increased,cell body enlarged and protuberance thickened and lengthened in hypothalamus of HFD group and HFD plus RYGB group.Compared with the HFD group,the number of Iba-1 and GFAP positive cells in hypothalamus of HFD plus RYGB group decreased.The neuronal mitochondrial edema,vacuole and a large number of autophagosomes were found in HFD group,and the neuronopathy alleviated in hypothalamus under electron microscope.Conclusions:RYGB can down-regulate the expressions of TNF-α,IL-1 and IL-6,alleviate the neuron lesion,improve the inflammatory response and reduce lipid accumulation in hypothalamus tissue of the obese rats induced by high fat diet.