CTRP13 attenuates the expression of LN and CAV-1 Induced by high glucose via CaMKKβ/AMPK pathway in rLSECs.

Objective: To investigate the effect and mechanism of CTRP13 on hepatic sinusoidal capillarization induced by high glucose in rat liver sinusoidal endothelial cells (rLSECs). Results: CTRP13 was reduced in high glucose-treated rLSECs. High glucose increased LN and CAV-1 expression and inhibited CaMKK beta and AMPK phosphorylation. CTRP13 overexpression protected rLSECs against high glucose-induced increase of LN and CAV-1 expression. Moreover, CTRP13 overexpression increased high glucose-induced inhibition of CaMKK beta and AMPK activation in CTRP13-overexpressing rLSECs. Inhibition of CaMKK beta and AMPK disturbed the protective effects of CTRP13 in high glucose-induced increase of LN and CAV1. Hepatic steatosis was enhanced and basement membrane was thickened in liver of diabetic fatty liver rats. Conclusions: Our data identified the protective role of CTRP13 in hepatic sinusoidal capillarization induced by high glucose via activating CAMKK beta/AMPK pathway. CTRP13 may be a potential target for screening and treating diabetic fatty liver. Methods: Construct lentiviral CTRP13 overexpression vector and transfect rLSECs. Use STO-609 (a CaMKK beta inhibitor) or Compound C (an AMPK inhibitor) to treat rLSECs. CTRP13, CaMKK beta, AMPK, laminin (LN) and caveolin-1 (CAV-1) were detected by qRT-PCR and Western blotting. Establish rat model of diabetic fatty liver. Use immunohistochemistry, hematoxylin-eosin and silver staining to observe the histopathological features of liver.