Study On The Role Of PRDM16 In Regulating Adipokine And Inhibiting Endothelial Inflammation Induced By High Glucose

Background: Changes in adipose tissue adipokine secretion can affect peripheral vascular function through paracrine.In normal bodies,adipokine can regulate peripheral vascular function by secreting anti-inflammatory adipokine.Diabetes mellitus(T2DM)causes adipose tissue dysfunction,and induces or aggravates endothelial inflammation and endothelial dysfunction.PRDM16 is a gene involved in the differentiation of brown fat,but no studies have shown its effect on adipokines.Objective: To investigate the effect of PRDM16 on inflammatory response of human umbilical vein endothelial cells(HUVEC)in high glucose environment by promoting the Browning of adipocytes and regulating adipokine levels.Methods: Western blot and RT-q PCR were used to detect the changes of inflammatory factors(IL-1β,IL-6,ICAM-1,TNF-α and MCP-1)in HUVEC cells cultured with high glucose(25m M)and conventional glucose(5.5m M).Confirm that high glucose promotes inflammatory changes in HUVEC cells;PRDM16 was transfected with lentivirus in adipocyte 3T3-L1,and the adipocyte differentiation was confirmed by oil red staining.Western blot and RT-q PCR were used to detect fat brown-related proteins and adiponectin changes(UCP-1,omentin-1,adiponectin)in differentiated adipocytes.The expression of inflammatory factors(IL-1β,IL-6,ICAM-1,VCAM-1,TNF-α and MCP-1)in HUVEC cells with high glucose injury were detected by Western blot and RT-q PCR.Results: Compared with normal glucose group,the expression of TNF-α,MCP-1,ICAM-1 and other inflammatory factors were increased in HUVEC cells in high glucose group,confirming the inflammatory response of HUVEC cells under high glucose environment.Compared with idling group,the expression levels of UCP-1,adiponectin and omentin-1 in PRDM16 overexpressing adipocytes were up-regulated.The expression of inflammatory factors such as TNF-α,MCP-1 and ICAM-1decreased in HUVEC cells with high glucose injury cultured in adipocyte conditioned medium overexpressing PRDM16.Conclusion: PRDM16 can up-regulate the expression level of anti-inflammatory adipokine and promote the Browning of adipocytes.Conditioned culture of PRDM16 overexpressed adipocytes can reduce endothelial inflammation induced by high glucose.