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

Lookup NU author(s): Professor Stuart McPhersonORCiD


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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 (rs = -0.28, p = 0.002), stage of fibrosis (rs = -0.375, p < 0.001) and severity of inflammation (rs = -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 HOMA ≤ 2 (p = 0.006) and NDL (p = 0.016). Conclusions: SREBP-1c may not play a prominent role in the pathogenesis of HCV-related steatosis. © 2008 European Association for the Study of the Liver.

Publication metadata

Author(s): McPherson S, Jonsson JR, Barrie HD, O'Rourke P, Clouston AD, Powell EE

Publication type: Article

Publication status: Published

Journal: Journal of Hepatology

Year: 2008

Volume: 49

Issue: 6

Pages: 1046-1054

ISSN (print): 0168-8278

ISSN (electronic): 1600-0641

Publisher: Elsevier BV


DOI: 10.1016/j.jhep.2008.06.022

PubMed id: 18752865


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