The Effect Of Survivin On Adipokines Leptin And ApoE Expression And Secretion

Objective: Survivin is a member of the anti-apoptotic proteins family.It is highly expressed in tumor and embryonic stem cells,and is extremely low in terminally differentiated cells.In our previous work,we found that the expression of Survivin in adipocytes continued to decrease as the differentiation progressed.High-fat diet can upregulate the expression of Survivin in mature adipocytes.After analyzing the RNA-seq database,we found that Leptin and ApoE may be regulated by Survivin,and this article will explore it further.Methods:(1)At the cellular level,we construct lentivirus-mediated Survivinoverexpressing 3T3-L1 adipocyte and SVFs cell transfection models;perform analysis of adipokines expression profile of the RNA-seq database;detect Leptin and ApoE expression levels.(2)At the animal level,we construct adeno-associated virus AAVmediated Survivin overexpression mice model by adipose tissue injection;we detect the Leptin and ApoE expression after giving normal or short-term high fat diet.Western blot and q PCR techniques were used to detect gene expression at the m RNA and protein levels,and ELISA was used to analyze the secretion of Leptin and adiponectin in cell culture supernatant and serum.Results: The results of transcriptome sequencing show that overexpression of Survivin in 3T3-L1 mature adipocytes can downregulate Leptin specifically.It was no significant change of the other 29 classical adipokines.And only ApoE expression changed significantly in apolipoprotein family members.Our studies also proved that overexpression of Survivin can down-regulate the expression and secretion of Leptin and ApoE in adipocytes,and there was no significant change in adiponectin expression.We overexpressed Survivin in the SAT,and give the mice normal diet.We found that the expression and secretion of Leptin were down-regulated.But the downward trend disappeared when we gave them short-term high-fat diet.There was no significant difference in the amount of food and weight of mice,and there was no significant downregulation of ApoE.Conclusion: At the cellular and animal levels,Survivin down-regulates the expression and secretion of Leptin,suggesting that Survivin may regulate systemic metabolism by Leptin.However,we only found the down-regulation of Survivin on the expression and secretion of ApoE at the cellular level,but not in vivo,which may be related to the various regulatory mechanisms of ApoE.