The Function And Regulation Techanism Of Neddylation E2 UBE2M In Obesity Induced Inflammation And Insulin Resistance

Metabolism and immune system are the basis of life survival,both are inseparable,any dysfunction will lead to chronic metabolic disorders.More and more studies have shown that chronic inflammation is closely related to metabolic diseases,especially in the occurrence and development of obesity and insulin resistance,and the regulation and plasticity of macrophages in chronic inflammation are thought to play a decisive role in this complex pathophysiological environment.Neddylation,as a new way of post-translational modification of proteins,has gradually become a hot research topic recent years.UBE2M is a key E2 enzyme in the process of Neddy lation,exploring the new function of macrophages in chronic inflammatory reaction and related metabolic diseases from the perspective of Neddylation,finding its endogenous regulatory molecules has become the key to the treatment of related metabolic diseases.The research found that UBE2M plays an important role in regulating the chronic inflammatory response of macrophages and affecting pathological processes such as obesity and insulin resistance.In the high-fat diet-induced obesity model,UBE2M macrophage-specific knockout mice are less obese,insulin resistance is weakened,and the body is more sensitive to insulin.At the same time,the knockdown of UBE2M alleviates the intensity of inflammatory response in adipose tissue and liver,and reduces the deposition of lipid droplets in the liver to alleviate hepatic steatosis and liver damage.In vitro and in vivo mechanisms have shown that the reduction of chronic inflammation and the remission of related metabolic diseases by UBE2M knockout are associated with the transcriptional regulation of IL-1?.Further studies have found that UBE2M knockdown can promote high expression of VHL and elongin B in macrophages,promotes the formation of the VHL E3 ubiquitin ligase complex,and accelerates the degradation of the IL-1?-specific transcription factor HIF-1?.Finally,the expression of inflammatory factor IL-1? was affected at the transcriptional level,which alleviated the progression of the disease.This study reveals for the first time that UBE2M affects obesity-related chronic inflammation and irsulin resistance by transcriptionally regulating IL-1?,innovatively proposed a new mechanism for UBE2M to regulate the chronic inflammatory response of macrophages,and provide new ideas for the treatment of inflamoation-related metabolic diseases from the perspective of Neddylation.