Berberine Improves Insulin Resistance Depending On SIRT1 In Adipose Tissue

Berberine(BBR)is the main active ingredient of Rhizoma Coptidis used to clear away heat and purge fire,can significantly reduce blood glucose and reduce weight,improve glucose tolerance and insulin resistance in vivo,but its exact target is not clear.Recent studies have found that berberine regulates insulin resistance by activating the AMPK pathway.SIRT1 is also involved in the AMPK signaling pathway,and its anti-inflammatory properties are closely related to insulin resistance.We have found that berberine and SIRT1 are basically consistent with the main targets and biological effects in regulating glycolipid metabolism.Therefore,by knocking out the SIRT1 gene in vivo,we observed whether the expression of insulin sensitivity-related signaling pathway in adipose tissue of mice changed after BBR administration,and whether BBR improves glucose metabolism and insulin resistance depends on SIRT1 to provide new clues to the mechanism of BBR.Purpose:The high fat diet,observed in vivo knockout SIRT1 mice adipose tissue,explore effects of BBR on the expression of glucose metabolism and insulin pathway related protein in adipose tissue is dependent on SIRT1 mediated.Method:1)The establishment of C57BL/6 and SIRT1?/? in high fat fed mice,14 weeks and related evaluation index replication model of obesity metabolism and insulin sensitivity index,while using BBR to drug intervention 15 days pharmacodynamic study.2)Western blot was used to detect the expression of SIRT1 in adipose tissue and the expression of AMPK,LKB1?ACC and AKT in glucose metabolism and insulin signaling pathway.3)The expression of SIRT1 in adipose tissue was detected by Real time PCR.4)Determination of acetylation of PGC-1?/FOXO1 by Co-immunoprecipitation.5)Detection of the expression of IL-1??IL-6?TNF-a and MCP-1 in Serum by ELISA.6)Western blot was used to detect the expression of P-JNK?P-IKK? in adipose tissue.Research results:1)After 12 weeks of high-fat diet,the body weight of wild-type and SIRT1?/? mice increased significantly,and the weight gain of SIRT1+/-mice was more significant after 11 weeks.2)After BBR administration,compared with SIRTI?/? mice,wild-type mice had decreased fasting blood glucose,weight loss,glucose tolerance and insulin tolerance.3)BBR can up-regulate the protein and gene expression of SIRT1 in wild-type mice mice and the 50mg/kg BBR is the most significant(P<0.05),but the change have been weakened in SIRT1?/-mice.4)BBR significantly increased the phosphorylation levels of AMPK?LKB1?ACC?AKT in adipose tissue of wild-type mice,but these effects were attenuated in SIRT1?/-mice.5)In the wild-type mice group,berberine decreased the acetylation of PGC-1? and FOXO1 in adipose tissue,but increased the acetylation of PGC-1? and FOXO1 in SIRT1 knockout group.6)BBR could reduce the expression of IL-1??IL-6?TNF-? and MCP-1,which was induced by fat accumulation in B6 mice,but these effects were attenuated in SIRT1+/-mice.7)Berberine can reduce the phosphorylation of JNK?IKK? in the inflammatory related pathway induced by fat accumulation,but these effects are attenuated in SIRT1+/-mice.Conclusion:Berberine can improve insulin resistance in adipose tissue by up-regulating SIRT1,activating AMPK/AKT pathway,regulating energy metabolism,and decreasing the activation of inflammatory protein associated with JNK/IKK?.