The Effect Of GGPPS Specific Deletion In Adipocytes On Adipokines Secretion

Adipose tissue is an endocrine organ which is closely related with energy metabolism.Adipokines can participate in many metabolic processes.The transportation of adipokines requires the vesicle transport system.Mevalonate pathway can prodece isoprenoid groups which can be used for post-translational modifications of some small GTP binding proteins,these proteins are closely related with vesicle transportation.GGPPS(Geranylgeranyl bisphosphate synthase)is used to produce isoprene groups.GGPPS catalyzes the synthesis of GGPP from FPP.The abnormal expression of this enzyme will affect the relative content of FPP and GGPP,and thus disrupts the balance between protein farnesylation and geranylgeranylation,which may interfere vesicle transportation of adipokines in adipose tissues.According to these,it is necessary for construction of the mice model about GGPPS specific deletion in adipose tissues.Selecting Ggpps-floxed mice with Loxp and GGPPS genes and a P2-Cre mice with fat cell specific promoter a P2 to hybridize to obtain the mice model of GGPPS specific deletion in adipose tissues.According to the genotyping of the mice,determing the model has Loxp and Cre genes at the same time.According to multi tissue RT-PCR and Western blot confirming that the expression of GGPPS in the adipose tissue is reduced and it has no change in other tissues.In this study,GGPPS+/+ and GGPPS-/-mice were divided into two groups and fed with chow diet and high-fat diet.We found that the body weight,tissues weight and cell diameter of GGPPS-/-mice were improved.Insulin sensitivity and glucose tolerance also reduced.In addition,the energy metabolism in high-fat diet of GGPPS-/-mice was reduced.The expression of Glut4 and leptin which closely related with vesicle transportation is also reduced in GGPPS-/-mice.These results can provides a new perspective for studying the pathogenesis of obesity related diseases.