Effects And Mechanism Of HMGB1 In Insulin Resistance Induced By High-fat Diet

HMGB1(high mobility group protein 1)is a non-histone that is ubiquitous in the chromosomes of eukaryotic cells.HMGB1 was first discovered as a late inflammatory factor to exert its biological activity to mediate and maintain inflammation.However,the mechanism of HMGB1 mediated insulin resistance in high-fat diet is not clear.In this study,we found that the mechanism of HMGB1 mediates insulin resistance in C57BL/6 male mice induced by high-fat diet.In vivo,we found that the high-fat diet induced indicators of insulin resistance(GTT and ITT,HOMA-IR)were abnormal,and The expression of HMGB1 in liver tissue of mice was significantly elevated and has correlation with the fat concentrations.And remission of insulin resistance after treatment with HMGB1 neutralizing antibody.Subsequently,we conducted an in-depth study of the mechanism of action of HMGB1 in insulin resistance.In vitro,we found that treatment with free fatty acids and HMGB1,significant insulin resistance can occur,and we further found that HMGB1 passes through IRS1-1101 serine Phosphorylation,which inhibits Akt phosphorylation,inhibits the insulin signaling pathway,and ultimately promotes the development of insulin resistance.In summary,this study found that HMGB1 is involved in the process of insulin resistance induced by high-fat diet.Effects and mechanism of HMGB1 was explored at the molecular level.