Effects Of Ketogenic Diet On Vascular Hyperpermeability In Diabetic Mice By Down-regulating PES1 Expression

Background: Previous reports implied a possible link between ketogenic diet and vascular permeability.However,the role of PES1 in regulating T2 DM related vascular permeability and the effect of ketogenic diet（KD）on PES1 have not been reported.The aim of present study is to explore the role of PES1 in effects of KD on diabetic mice and its mediated mechanism.Methods: Male C57BL/6J and db/db mice were fed with standard diet（SD）and KD,respectively.Simultaneously,MVEC cells were treated by β-hydroxybutyric acid（β-HB）.Additionally,systemic knockout（SKO）of Pes1 in vivo was applied.Results: Vascular PES1 expression in diabetic mice was markedly increased,which was suppressed by KD feeding.In mice with KO of Pes1,the protein levels of VE-cadherin,Angiopoietin-1 and Occludin were upregulated in blood vessels,and the VEGF were decreased.The similar outcomes were also observed in β-HB treated-and Pes1 knockdown-MVEC cells.In vitro and in vivo permeability tests showed that monolayer cellular permeability and vascular permeability were respectively decreased after β-HB treatment and KD feeding.Conclusion: KD may decrease vascular hyperpermeability in type 2 diabetic mice by down-regulating PES1 expression.