Article first published online: 15 FEB 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 5, pages 1697–1704, May 2013
How to Cite
Lambert, J. E., Bain, V. G., Ryan, E. A., Thomson, A. B.R. and Clandinin, M. T. (2013), Elevated lipogenesis and diminished cholesterol synthesis in patients with hepatitis C viral infection compared to healthy humans. Hepatology, 57: 1697–1704. doi: 10.1002/hep.25990
Potential conflict of interest: Nothing to report.
See Editorial on Page 1684
Project funding (to P.I. M.T.C.) was provided by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada. A training scholarship (to J.E.L.) was provided by the Canadian Institutes of Health Research.
- Issue published online: 22 APR 2013
- Article first published online: 15 FEB 2013
- Accepted manuscript online: 1 AUG 2012 07:36AM EST
- Manuscript Accepted: 11 JUL 2012
- Manuscript Received: 5 MAR 2012
Hepatitis C virus (HCV) exerts a profound influence on host lipid metabolism. It has been suggested that the synthesis of both fatty acids (FA) and cholesterol is dysregulated in HCV but this has not been directly quantified in humans. The purpose of this study was to measure lipogenesis and cholesterol synthesis using stable isotopes in patients with HCV (n = 5) and healthy control (n = 9) subjects recruited from the University of Alberta hospital. Blood samples were taken at fasting (0 and 24 hours) and after meals over the day to mimic typical food consumption and postprandial metabolism. Isolation of free cholesterol (FC), cholesteryl ester (CE), and triglyceride (TG) from plasma and very low-density lipoproteins (VLDL) was used to measure FA and cholesterol synthesis using deuterium uptake and isotope ratio mass spectrometry. FA composition was analyzed by gas chromatography. VLDL-TG levels of polyunsaturated fatty acids (PUFA), including linoleic and linolenic acid, were lower in HCV compared to control (P < 0.05 for both). Fasting hepatic lipogenesis was significantly higher in HCV (2.80 ± 0.55%) compared to control (1.19 ± 0.27%; P = 0.03). Conversely, fasting whole-body synthesis of FC (HCV 1.64 ± 0.28% versus control 8.78 ± 1.59%) and CE (HCV 0.26 ± 0.08% versus control 1.92 ± 0.25%), as well as hepatic FC synthesis (HCV 1.68 ± 0.26% versus control 8.12 ± 0.77%) was lower in HCV (P < 0.001 for all). Conclusion: These data provide evidence that lipogenesis is elevated while cholesterol synthesis is impaired in HCV, supporting previous findings from cellular and animal models. Low PUFA levels combined with elevated lipogenesis suggests a role for dietary PUFA supplementation in HCV patients. (HEPATOLOGY 2013)