CTRP13 Attenuates Hepatic Sinusoidal Endothelial Cell Dysfunction Induced By High Glucose Through CaMKK?/AMPK Signaling Pathway

Objective This study was to investigate the effect and mechanism of C1q/TNF-related protein 13(CTRP13),a novel adipokine,on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells(rLSECs).Methods Culture rLSECs.Construct lentiviral CTRP13 overexpression vector(LV-CTRP13)and transfect rLSECs with LV-CTRP13.The rLSECs treated by STO-609(a CaMKK? specific inhibitor)and Compound C(an AMPK specific inhibitor),respectively.CTRP13,Calcium/calmodulin-dependent protein kinase kinase beta(CaMKK?),AMP-activated protein kinase(AMPK),laminin(LN)and caveolin-1(CAV-1)were detected by qRT-PCR and Western blotting.Establish rat model of diabetic fatty liver disease.Use hematoxylin-eosin(HE)staining and gomori methenaminutese silver staining to observe the histopathological features of liver.Use immunohistochemical assay to detect CTRP13 expression of liver.Results CTRP13 was reduced in high glucose-treated rLSECs.LN and CAV-1 were increased in high glucose-treated rLSECs.Treatment with lentiviral CTRP13 overexpression vector(LV-CTRP13)attenuated high glucose-induced increase of LN and CAV-1 expression in rLSECs.Moreover,CTRP13 overexpression increased high glucose-induced inhibition of CaMKK? and AMPK activation in CTRP13-overexpressing rLSECs.Inhibition of CaMKK? and AMPK phosphorylation disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV-1 expression.Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats.Immunohistochemical staining showed that CTRP13 was reduced in the liver from diabetic fatty liver rats.Conclusions Under high glucose conditions,the down-regulation of CTRP13 can induce the dysfunction of hepatic sinusoidal endothelial cells by up-regulating the expression of LN and CAV-1 through the CaMKK?/AMPK signaling pathway,thereby promoting hepatic sinusoidal capillary vascularization.CTRP13 may be a potential target for screening and treating diabetic fatty liver.