The Role And Regulation Of TAZ During Adipogenesis

As people’s life quality is improved, the number of patients with excessive body weight is larger and larger. More and more people are with diseases of diabetes, hypertension and hyperlipemia, which decrease their life quality. There is significance to do research on obesity and to search for methods of control ing and curing.Obesity is defined as an excessively high amount of body fat or adipose tissue in relation to lean body mass. Both environment and genetic factors contribute to overweight and obesity. The gain of weight is due in part to an increase in the number of adipocytes. This hyperplasia results from the recruitment of pluripotent stem cells present in the vascular stroma of adipose tissue.TAZ is a transcriptional factor interacted with14-3-3protein, founded in2000. TAZ regulates the development of bone, muscle, adipose, lung, heart, limbs, etc. In2005, Jeong-Ho Hong found that TAZ is a modulator of mesenchymal stem cell differentiation, who coactivates Runx2-dependent gene transcription while repressing PPAR γ-dependent gene transcription. But apart from PPAR family, C/EBP family and SREBP family also participate in the regulation of adipogenesis. The role of TAZ in adipogenesis and the regulation signaling pathway are not clear. In this article, we observed the expression of TAZ in the process of3T3-L1preadipocytes differentiation and focused on factors affecting its expression and found a new mechanism that TAZ regulated differentiation of adipocytes.We found that there was no obvious change of TAZ expression in dividing3T3-L1cells. But the expression of TAZ decreased early after induction and then increased till the end of differentiaon. This fact gave us a hint that the change of TAZ expression was significant to adipogenesis and some important factors affected the maturation of adipocyte via regulating the expression of TAZ.It is the pivotal time point for adipocyte differentiation when the expression of TAZ changed in the early time of adipocyte induction. To search for the mechanism of TAZ regulating adipogenesis, we constructed a retrovirus expression vector and overexpressed TAZ in3T3-L1. The result was that TAZ overexpression inhibited the differentiation of3T3-L1cells. We assumed that the decreacse of TAZ in the early time of adipogenesis was important. This change of TAZ expression was triggered by the addition of Mix/Dex/Ins inducers to the postconfluent cells. Then we tested the expression of TAZ after adding different goups of inducers to cells and found that dexmethasone (Dex) caused the decrease of TAZ expression, which indicated the important role of Dex in regulating the expression of TAZ. To research the mechanism of Dex regulating the expression of TAZ further, we treated3T3-L1cells with different concentrations of Dex for6hours and found that the high concentration caused the decrease of TAZ expression while the low concentrations had no effect.DEX, a synthetic glucocorticoid, can induce osteoporosis and even pathologic fracture when it is administrated at long-term and over-dose. DEX has been revealed to inhibit osteoblastic differentiation through the repression of BMP-2expression, which in turn leads to a decrease in bone formation, and DEX redirect the differentiation of bone marrow stromal cells from the osteoblastic lineage to the adipocyte lineage. However, most studies argue that DEX in vitro enhances the osteoblastic differentiation, alkaline phosphatase activity and bone mineralization. DEX enhanced osteoblastic differentiation and increased TAZ expression in MSCs depending on its concentration in culture medium. We presumed that Dex might play a likely role in our study. Then we tested some gene markers of osteoblasts (Runx2, osteocalcin, osteorix, etc.) and found that the expression of osteoblast genes were inhibited as the concentration of Dex was increased. This result demonstrated that high concentration of Dex inhibited3T3-L1cells differentiating into osteoblastic lineage by decreasing the expression of TAZ and some markers of osteoblasts and promoted the differention of preadiopcytes to mature adipocytes. Our research provides a new explaination that Dex induces osteoporosis and even pathologic fracture when it is administrated at long-term and over-dose.But how does Dex regulate the expression of TAZ? We tried to test the effect of Dex on the stability of TAZ mRNA according to some reports and found that Dex indeed decreased the mRNA stability of TAZ. But which signaling pathway controlled this process was not clear, and more work has to do in the future.