Synergism between loss of von hippel-lindau protein and nutritional cholesterol intake promotes nonalcoholic steatohepatits

Abstract

Systemic hypoxia is associated with an increase in cholesterol levels, which confers at higher risk for coronary heart disease. In addition, increased hepatic cholesterol has emerged as a important player in nonalcoholic fatty liver disease promoting the transition from steatosis to nonalcoholic steatohepatitis (NASH). As steroidogenic acute regulatory protein (STARD1) has been recently shown to promote NASH progression towards hepatocellular carcinoma (HCC) and its expression is regulated byhypoxia, our aim was to investigate the interplay between hypoxia signaling and the nutritional intake of cholesterol in the progression of NASH in mice with hepatocyte-specific deletion of von Hippel-Lindau (VHL) protein, an E3 ubiquitin ligase required for HIF degradation.