Biomarkers of NAFLD progression: A lipidomics approach to an epidemic 1

D. Lee Gorden, David S. Myers, Pavlina T. Ivanova, Eoin Fahy, Mano R. Maurya, Shakti Gupta, Jun Min, Nathanael J. Spann, Jeffrey G. McDonald, Samuel L. Kelly, Jingjing Duan, M. Cameron Sullards, Thomas J. Leiker, Robert M. Barkley, Oswald Quehenberger, Aaron M. Armando, Stephen B. Milne, Thomas P. Mathews, Michelle D. Armstrong, Chijun LiWillie V. Melvin, Ronald H. Clements, M. Kay Washington, Alisha M. Mendonsa, Joseph L. Witztum, Ziqiang Guan, Christopher K. Glass, Robert C. Murphy, Edward A. Dennis, Alfred H. Merrill, David W. Russell, Shankar Subramaniam, H. Alex Brown

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)722-736
Number of pages15
JournalJournal of lipid research
Volume56
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Diagnostic tools
  • Mass spectrometry
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis
  • Phospholipids
  • Sphingolipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Gorden, D. L., Myers, D. S., Ivanova, P. T., Fahy, E., Maurya, M. R., Gupta, S., Min, J., Spann, N. J., McDonald, J. G., Kelly, S. L., Duan, J., Sullards, M. C., Leiker, T. J., Barkley, R. M., Quehenberger, O., Armando, A. M., Milne, S. B., Mathews, T. P., Armstrong, M. D., ... Brown, H. A. (2015). Biomarkers of NAFLD progression: A lipidomics approach to an epidemic 1. Journal of lipid research, 56(3), 722-736. https://doi.org/10.1194/jlr.P056002