The Mechanism Research Of Ajuba Source Peptide Control

As life level is improving, people input more energy than they can output, and the excessive energy is stored in adipose tissue and ultimately give rise to obesity. A large amount research implicate the obesity is high related to many metabolic diseases, like cardiovascular diseases and type II diabetes, which attracts more and more attention and research. The nuclear receptor family Peroxisome Proliferator Activated Receptor(PPAR), particularly PPAR? plays the indispensible and master role in adipogenesis and maintaining the adipose tissue function. Most metabolic drugs are targeting PPAR?. Our previous research uncovered the LIM protein Ajuba was essential in adipogenesis through docking to PPAR? as a coactivator. In this research, we further recognized the NO.309-329 AA in mouse Ajuba protein was responsible to the interaction with the DNA binding domain of PPAR?. Surprisingly, we also noticed this sequence containing two conserved Ser-sites which can be phosphorylated by ERK family kinase. Under EGF treatment, the interaction between Ajuba and PPAR? was enhanced. We also synthesized the peptides identical to the interaction-sequence, and confirmed the peptides could directly interact with the DNA binding domain of PPAR? in vivo. In 3T3L1 preadipocytes, the treatment of the peptides could effectively inhibite the expression of PPAR? targets by blocking the interaction between Ajuba and PPAR?. Further investigation suggested the peptides also modestly inhibited the adipogenesis of 3T3L1.In our research, we figured out a new peptides targeting to PPAR? activity. This peptides could effectively inhibites adipocytes differentiation through competing with Ajuba for the interaction with PPAR? and removing the co-activating effect on PPAR? transcriptional activity. Our present and further research may offer a potential drug for treating obesity.