Role of glycoprotein 78 and cidec in hepatic steatosis

Abstract

Hepatic glycoprotein (gp78), a membrane-anchored E3 ubiquitin ligase, has been reported to be involved in regulating lipid and energy metabolism in animals, and cell death-inducing DFFA-like effectorc (cidec) has emerged as an important regulator of metabolism, which has been implicated in the process of fat differentiation. Nonalcoholic fatty liver disease is a metabolic disorder associated with hepatic steatosis. In the present study, to investigate the role of gp78 and cidec in hepatic steatosis, an in vitro cell culture model of hepatic steatosis was established, using the AML12 mouse hepatocyte cell line to assess the protein expression of gp78. The results of Oil Red O staining, phase contrast microscopy and triglyceride content detection experiments indicated that the overexpression of gp78 induced lipid accumulation, whereas gp78-knockdown led to a reduction in lipid accumulation in the AML12 cells. The increased expression of gp78 was associated with steatosis. The expression of cidec was consistent with gp78, and the colocalization of gp78 and cidec was observed on the surface of lipid droplets using im munofluorescence a na lysis. Furthermore, an interaction between gp78 and cidec was detected using coimmunoprecipitation analysis, and this interaction promoted lipid accumulation. Based on these data, it was hypothesized that gp78 is a regulator of hepatic steatosis, and that it may be a putative molecular mediator in metabolic diseases.