Investigation of the role of SREBP-1c in the pathogenesis of HCV-related steatosis.

BACKGROUND/AIMS: Increased expression of sterol regulatory element binding protein (SREBP)-1c, a transcription factor regulating lipogenesis, has been reported in HCV core protein-transfected hepatocytes. Our aim was to investigate the role of SREBP-1c in the pathogenesis of HCV-related steatosis.

METHODS: One hundred and twenty-four patients with HCV and 13 subjects with histologically normal liver (NDL) were studied. The mRNA expression of SREBP-1c, fatty acid synthase (FAS), glycerol-3-phosphate acyltransferase (GPAT) and microsomal triglyceride transfer protein (MTP) was measured by qPCR, and SREBP-1 protein quantitated by immunohistochemistry.

RESULTS: There was no significant difference in the hepatic expression of SREBP-1c mRNA between subjects with HCV and NDL. In patients with HCV, a significant negative relationship was seen between hepatic SREBP-1c mRNA expression and grade of steatosis (r(s)=-0.28, p=0.002), stage of fibrosis (r(s)=-0.375, p<0.001) and severity of inflammation (r(s)=-0.313, p<0.001). These relationships were observed for patients infected with either viral genotype 1 or 3. Following multivariate logistic regression analysis, hepatic SREBP-1c expression remained independently associated with fibrosis (p=0.008) and hepatic inflammation (p=0.005). HCV-infected patients with HOMA>2 had significantly higher expression of FAS mRNA than HCV-infected subjects with HOMA2 (p=0.006) and NDL (p=0.016).

CONCLUSIONS: SREBP-1c may not play a prominent role in the pathogenesis of HCV-related steatosis.