The plasma lipidomic signature of nonalcoholic steatohepatitis
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UNLABELLED: 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 gamma-linolenic (18:3n6) and dihomo gamma-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.
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Lipid analysis in patients with MASH shows that palmitic, stearic, and oleic acids remain the main components of the circulating FFA pool.
“At the same time, lipid analysis in patients with MASH shows that palmitic, stearic, and oleic acids remain the main components of the circulating FFA pool [147].”
From The HepG2 Cell Line as a Model for Studying Metabolic Dysfunction-Associated Steatotic Liver Disease (2026) · cites this paper as [147]
PC and LPC, particularly PC(22:0, 20:4) and LPC(16:0,18:0), were found to be reduced in several studies, while LPC (16:0, 16:1, 18:1, 20:0, 20:1) were increased in others or increased in MASL and reduced in MASH.
“In fact, PC and LPC, particularly PC(22:0, 20:4) and LPC(16:0,18:0), were found to be reduced in several studies,107,109,110,112 while LPC (16:0, 16:1, 18:1, 20:0, 20:1) were increased in others102,108,111,113 or increased in MASL and reduced in MASH.94”
From Lipid metabolism in MASLD and MASH: From mechanism to the clinic (2024) · cites this paper as [110]
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- Authors
- Puri, P., Wiest, M. M., Cheung, O., Mirshahi, F., Sargeant, C., Min, H., Contos, M. J., Sterling, R. K., Fuchs, M., Zhou, H., Watkins, S. M., & Sanyal, A. J.
- Affiliations
- Virginia Commonwealth University Medical Center (US)
- Virginia Commonwealth University (US)
- Corresponding author
- Sanyal, Arun J.
- ORCID
- Venue
- Hepatology
- Published
- 2009-12
- Volume
- 50
- Issue
- 6
- Pages
- 1827-1838
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC5031239
- OpenAlex
- W1998323589
- Cited by
- 655
- References
- 36
- Citations by year
- 2026: 24 · 2025: 36 · 2024: 39 · 2023: 35 · 2022: 43 · 2021: 57 · 2020: 67 · 2019: 45 · 2018: 50 · 2017: 41 · 2016: 41 · 2015: 25 · 2014: 40 · 2013: 28 · 2012: 33
- FWCI
- 18.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (R01 56331-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK002755, T32DK007150, R01DK081410, K 24DK 02755-06, T32 DK07150-31)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, plasma lipidome, eicosanoids, monounsaturated fatty acids, palmitoleic acid, oleic acid, linoleic acid, gamma-linolenic acid, docosahexaenoic acid, plasmalogens, lipoxygenase metabolites, 5-hydroxyeicosatetraenoic acid, arachidonic acid oxidation, disease progression biomarkers, phospholipids
- MeSH terms
- Diglycerides, Fatty Acids, Nonesterified, Fatty Acids, Unsaturated, Fatty Liver, Female, Humans, Lipids, Male, Phospholipids, Triglycerides, Arachidonic Acid, Lipogenesis, Metabolomics
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