Protein Kinase MST3 Protects Against Obesity-Induced Inflammation And Insulin Resistance

Obesity has become a more and more serious global problem that has plagued people's lives.It produces a series of chronic inflammation reactions which leads to insulin resistance and even type 2 diabetes(T2D).The serine/threonine protein kinase MST3(STK24)is a member of the serine/threonine kinase family and involved in the regulation of cell migration,apoptotic protease-dependent or non-dependent apoptosis.In this study,we found that MST3 protected against obesity-induced inflammation and insulin resistance.In adipose tissue of obesity and obese diabetic patients,we found a significant decrease in the expression of MST3 compared to lean control subjects.In the high-fat diet-induced obesity model,MST3-deficient mice developed severer insulin resistance and a series of adipose pathological changes.We further found the activation of NLRP3 inflammasome in adipose tissue was significantly enhanced.Bone marrow reconstitution experiments showed that MST3 deficiency in the hernatopoietic system promoted the pathological changes induced by high fat diet.In vitro studies have shown that MST3 inhibited the activation of NLRP3 inflammasome in mouse peritoneal macrophages in kinase independent manner.We further found that MST3 specifically binded to NLRP3,and inhibited the assembly process of NLRP3 inflammasome.Intriguingly,inflammasome activation induced MST3 transferred from cytoplasm to nucleus.Summary,our study revealed that MST3 affected obesity-induced inflammation and insulin resistance by regulating the activation of NLRP3 inflammasome,this may provide a new idea for the treatment of some complications even diabetes caused by obesity and diabetes.