Steatohepatitis/Metabolic Liver Disease
Article first published online: 10 AUG 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 50, Issue 6, pages 1827–1838, December 2009
How to Cite
Puri, P., Wiest, M. M., Cheung, O., Mirshahi, F., Sargeant, C., Min, H.-K., Contos, M. J., Sterling, R. K., Fuchs, M., Zhou, H., Watkins, S. M. and Sanyal, A. J. (2009), The plasma lipidomic signature of nonalcoholic steatohepatitis. Hepatology, 50: 1827–1838. doi: 10.1002/hep.23229
Presented in part at the annual meeting of the American Association for Study of Liver Diseases (AASLD) in Boston, 2007.
Potential conflict of interest: Dr. Wiest is a consultant for and Dr. Watkins owns stock in Lipomics.
- Issue published online: 20 NOV 2009
- Article first published online: 10 AUG 2009
- Accepted manuscript online: 10 AUG 2009 12:00AM EST
- Manuscript Accepted: 30 JUL 2009
- Manuscript Received: 16 APR 2009
- National Institutes of Health. Grant Numbers: K24 DK 02755-06, T32 DK 07150-31, RO1 56331-05
Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty liver disease (NAFLD), which extends from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). However, the plasma lipidome of NAFLD and whether NASH has a distinct plasma lipidomic signature are unknown. A comprehensive analysis of plasma lipids and eicosanoid metabolites quantified by mass spectrometry was performed in NAFL (n = 25) and NASH (n = 50) subjects and compared with lean normal controls (n = 50). The key findings include significantly increased total plasma monounsaturated fatty acids driven by palmitoleic (16:1 n7) and oleic (18:1 n9) acids content (P < 0.01 for both acids in both NAFL and NASH). The levels of palmitoleic acid, oleic acid, and palmitoleic acid to palmitic acid (16:0) ratio were significantly increased in NAFLD across multiple lipid classes. Linoleic acid (8:2n6) was decreased (P < 0.05), with a concomitant increase in γ-linolenic (18:3n6) and dihomo γ-linolenic (20:3n6) acids in both NAFL and NASH (P < 0.001 for most lipid classes). The docosahexanoic acid (22:6 n3) to docosapentenoic acid (22:5n3) ratio was significantly decreased within phosphatidylcholine (PC), and phosphatidylethanolamine (PE) pools, which was most marked in NASH subjects (P < 0.01 for PC and P < 0.001 for PE). The total plasmalogen levels were significantly decreased in NASH compared with controls (P < 0.05). A stepwise increase in lipoxygenase (LOX) metabolites 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 8-HETE, and 15-HETE characterized progression from normal to NAFL to NASH. The level of 11-HETE, a nonenzymatic oxidation product of arachidonic (20:4) acid, was significantly increased in NASH only. Conclusions: Although increased lipogenesis, desaturases, and LOX activities characterize NAFL and NASH, impaired peroxisomal polyunsaturated fatty acid (PUFA) metabolism and nonenzymatic oxidation is associated with progression to NASH. (HEPATOLOGY 2009;50:1827–1838.)