Patient-Oriented and Epidemiological Research
Biomarkers of NAFLD progression: a lipidomics approach to an epidemic1[S]

https://doi.org/10.1194/jlr.P056002Get rights and content
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The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and cirrhosis. Recognition and timely diagnosis of these different stages, particularly NASH, is important for both potential reversibility and limitation of complications. Liver biopsy remains the clinical standard for definitive diagnosis. Diagnostic tools minimizing the need for invasive procedures or that add information to histologic data are important in novel management strategies for the growing epidemic of NAFLD. We describe an “omics” approach to detecting a reproducible signature of lipid metabolites, aqueous intracellular metabolites, SNPs, and mRNA transcripts in a double-blinded study of patients with different stages of NAFLD that involves profiling liver biopsies, plasma, and urine samples. Using linear discriminant analysis, a panel of 20 plasma metabolites that includes glycerophospholipids, sphingolipids, sterols, and various aqueous small molecular weight components involved in cellular metabolic pathways, can be used to differentiate between NASH and steatosis. This identification of differential biomolecular signatures has the potential to improve clinical diagnosis and facilitate therapeutic intervention of NAFLD.

diagnostic tools
mass spectrometry
phospholipids
sphingolipids
nonalcoholic fatty liver disease
nonalcoholic steatohepatitis

Cited by (0)

This work was primarily supported by National Institutes of Health Grant GM U54069338 to the LIPID MAPS Consortium. The authors declare no competing interest.

    Abbreviations:

    CE

    cholesteryl ester

    DAG

    diacylglycerol

    ECM

    extracellular matrix

    FDR

    false discovery rate

    F16BP

    fructose-1,6-bisphosphate

    GO

    gene ontology

    GPL

    glycerophospholipid

    HCC

    hepatocellular carcinoma

    KEGG

    Kyoto Encyclopedia of Genes and Genomes

    LDA

    linear discriminant analysis

    LPE

    lysophosphatidylethanolamine

    MMP

    matrix metalloproteinase

    MRM

    multiple reaction monitoring

    NAFLD

    nonalcoholic fatty liver disease

    NASH

    nonalcoholic steatohepatitis

    PC

    phosphatidylcholine

    PE

    phosphatidylethanolamine

    RNA-Seq

    RNA sequence

    S/N

    steatosis/normal

    SOP

    standard operating procedure

    TAG

    triacylglycerol

    TCA

    the citric acid or tricarboxylic acid cycle

[S]

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of seven figures, four tables, and five data files.

1

Guest editor for this article was Arthur A. Spector, University of Iowa (Emeritus).