The Role Of SIRT6 In Synthesis And Secretion Of Adropin

Rationale: The incidence of obesity and type 2 diabetes is increasing year by year,there is no ideal treatment for them so far.Changes in lifestyle such as high calorie diet and reduced exercise load are paramount facts that lend to the incident of obesity and diabetes.Recent studies have discovered that the expression of SIRT6 and adropin is increasing by some situations such as calorie restriction diet and aerobic exercise.It is a low serum concentration of adropin and a decline of SIRT6 in liver among obese patients.SIRT6 and adropin play an important role in energy metabolism by regulating lipid metabolism and insulin sensitivity,which may be a new target for the treatment of obesity and diabetes.However,there is no research yet to report the link between them.Objectives: To identify the relationship and possible mechanism between SIRT6 and adropin,as well as the regulation of related lipid metabolism molecules.Methods: Hep G2 cells were transfected with adenovirus-SIRT6.The expression of SIRT6 was detected by Western Blot,and the cell model of overexpression SIRT6 was established.The cells were divided into four groups: blank control group,the overexpression of SIRT6 cell group,normal cell + PA(Palmitic acid)group,the overexpression of SIRT6 cells +PA group.The concentration of adropin in the supernatant of culture medium was detected by ELISA kit.The content of adropin in cells was detected by Western Blot,and the m RNA of adropin-related genes(Enho)and its upstream factors such as RXR? and LXR? were detected by q PCR.To detect the changes in m RNA levels of some lipid metabolism molecules such as CD36,APOE,LIPE and SREBP2.Results: Hep G2 cells were added with adenovirus-SIRT6 for 24 h and SIRT6 was overexpressed.The secretion of adropin was increased in the supernatant of overexpressed SIRT6 cells,and is higher after added with PA.There was no significant change in the level of adropin in supernatant between the control group and PA treatment group.The overexpressed SIRT6 can enhance the synthesis of adropin,in which are increased significantly in PA intervention group,while the blank group after PA added also increased;the cells with SIRT6 overexpressed have no change in the transcription level of CD36,SREBP2,LIPE and APOE,but can enhance PA-induced expression of these genes.Conclusions: The synthesis and secretion of adropin are regulated by SIRT6: the overexpression of SIRT6 can increase the expression and secretion of adropin,which are not enhanced by PA.the regulation between SIRT6 and adropin may independent of LXR? and RXR?.The expression of CD36,APOE,LIPE and SREBP2 induced by PA was enhanced by the overexpression of SIRT6.