A Preliminary Exploration Of Adp On Adipogenesis

In recent years,with the increasingly obesity rate around the world,the obesity which is induced by an imbalance between energy intake and consumption begins to surpass undernutrition and infectious diseases as the most significant threat to health.Furthemore,the obesity may even increase the incidence of diabetes,cardiovascular disease,and cancer,bringing a great threat to human health.Adipose(Adp)is an evolutionarily conserved antiobesity gene with dosage-sensitive.Studies have confirmed that Adp can inhibit the fat formation of worm,fly and murine.The overexpression of Adp in 3T3-L1 cells can block adipocyte differentiation,while inhibit the expression of Adp can stimulate differentiation.It is reported that the substrate receptors of DDB1-CUL4 ubiquitin system are more than 30 kinds,18 of them are DCAFs which include 14 containing WD40 repeats.Adp is one of the substrate receptors of DDB1-CUL4 ubiquitin system.Adp possesses 6 WD40 repeats which interact with DDB1 through the 165th and 215th arginine.Adp work as a substrate adaptor in the DDB1-CUL4 ubiquitin system which regulates the stability of substrate protein to inhibit adipocyte differentiation.In this study,we confirmed Adp is a component of DDB1-CUL4 ubiquitin system.The overexpression of Adp in 3T3-L1 cells can block adipocyte differentiation,while the arginine mutants which can t interact with DDB1 stimulate adipocyte differentiation.We then found that Adp affects adipogensis between day 1 to day 2 during 3T3-L1 diffrentiation.Purification of Adp-interacting proteins suggested that Mybbpla could be a potential target of Adp-DDB1-CUL4 ubiquitin system.Knockdown of Mybbpla inhibits 3T3-L1 diffemtiation.We are currently working on how the stability of Mybbpla is regulated by the Adp-DDB1-CUL4 ubiquitin system.Conclusively,a potential approach of regulating Mybbpla and correspondingly inhibiting adipocyte differentiation is demonstrated through DDB1-CUL4 ubiquitin system.The results revealed the molecular mechanism of Adp which provides a potential new approach for the obesity and relevant metabolic diseases.