Sleeve Gastrectomy Reduces Lipid Accumμlation And Inhibits Activity Of Microglia And Astrocytes In The Hypothalamus In Rats With High-fat Diet-induced Obesity

Background:Obesity is associated with a generalized systemic inflammation,which occurs not only in peripheral tissues,but also in the hypothalamus.Bariatric surgery had proven to be an effective treatment,and its beneficial effects on body weight or insulin levels.However,the molecular mechanisms remains to be elucidated.The purpose of our study was to investigate the effect of sleeve gastrectomy(SG),a bariatric surgery,on hypothalamic injury and lipid accumulation in the brain tissue of rats with high-fat diet(HFD)-induced obesity.Methods:Sprague-Dawley(SD)rats were random Ly divided into HFD+Sham group,and HFD+SG group.All rats were fed a HFD for 6 months.After 6 months,rats underwent either Sham operation in the HFD+Sham group,or SG in the HFD+SG group,and then continued to be fed a HFD for 6 weeks.The concentrations of serum triglyceride(TG),total cholesterol(TC),free fatty acid(FFA),leptin,ghrelin,peptide YY(PYY),glucagonlike peptide-1(GLP-1),and plasma insulin,as well as the levels of diacylglycerol(DAG)and FFA in hypothalamus tissue were also determined by enzyme linked immunosorbent assay(Elisa).Expression levels of ionized calcium binding adaptor molecule 1(Iba-1),a marker of microglial activation,and glial fibrillary acidic protein(GFAP),a marker of reactive astrocytes,in hypothalamus were observed by immunohistochemistry and western blotting.At the time of sacrifice,rats were perfused with picric acid,and their brains were processed for electron microscopic examination.Expression levels of heat shock protein(HSP)72,JNK and P-P65 in the hypothalamus were detectd by western blotting.Results:The resμLts showed that compared to HFD+Sham group,total body weight and homeostatic model assessment of insulin resistance(HOMA-IR)were decreased in HFD+SG group(P<0.05).Serum levels of TG,TC,Leptin,Ghrelin,PYY,FFA and INS in HFD+SG group were significantly decreased 6 weeks after surgery(P<0.05).GLP-1level was significantly decreased in HFD+SG group(P<0.05).Significantly decreased levels of hypothalamic DAG and FFA were also observed between the two groups(P<0.05).The levels of Iba-1 and GFAP were significantly lower in HFD+SG group than that in HFD+Sham group.Pathological changes in the mitochondria,cytoplasm,and autophagosomes of cells in the hypothalamus were observed in HFD+Sham group.Pathological changes in the cytoplasm and mitochondria were less severe in HFD+SG group(P<0.05).Expression levels of HSP-72,p-JNK and p-P65 in hypothalamic tissues were lower in HFD+SG group than those in HFD+Sham group(P<0.05).Conclusion: The results of this study suggested that SG reduced lipid accumulation and inhibited the activity of microglia and astrocytes in the hypothalamus induced by a HFD,which may be associated with downregμLation of the JNK and NF-κB inflammation signaling pathway.Figure 7 Table 15 Reference 116...