Abstract

Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes. In addition, β-oxidation regulatory genes are upregulated by PRR inhibition to attenuate liver lipid content and liver steatosis. This evidence suggests that targeting the dysregulated hepatic PRR may be effective in reducing liver steatosis postliver transplantation.

Keywords: Prorenin receptor, nonalcoholic fatty liver disease, liver metabolic alteration, liver transplantation, mammalian target of rapamycin, peroxisome proliferator-activated receptor.