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

96 Citations (Scopus)

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

Fingerprint

Biomarkers
Liver
Disease Progression
Metabolites
Biopsy
Glycerophospholipids
Plasmas
Sphingolipids
Discriminant analysis
Sterols
Discriminant Analysis
Metabolic Networks and Pathways
Non-alcoholic Fatty Liver Disease
Single Nucleotide Polymorphism
Molecular weight
Fibrosis
Lipids
Molecular Weight
Messenger RNA
Urine

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Gorden, D. L., Myers, D. S., Ivanova, P. T., Fahy, E., Maurya, M. R., Gupta, S., ... 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

Biomarkers of NAFLD progression : A lipidomics approach to an epidemic 1. / Gorden, D. Lee; Myers, David S.; Ivanova, Pavlina T.; Fahy, Eoin; Maurya, Mano R.; Gupta, Shakti; Min, Jun; Spann, Nathanael J.; McDonald, Jeffrey G.; Kelly, Samuel L.; Duan, Jingjing; Sullards, M. Cameron; Leiker, Thomas J.; Barkley, Robert M.; Quehenberger, Oswald; Armando, Aaron M.; Milne, Stephen B.; Mathews, Thomas P.; Armstrong, Michelle D.; Li, Chijun; Melvin, Willie V.; Clements, Ronald H.; Washington, M. Kay; Mendonsa, Alisha M.; Witztum, Joseph L.; Guan, Ziqiang; Glass, Christopher K.; Murphy, Robert C.; Dennis, Edward A.; Merrill, Alfred H.; Russell, David W.; Subramaniam, Shankar; Brown, H. Alex.

In: Journal of Lipid Research, Vol. 56, No. 3, 01.03.2015, p. 722-736.

Research output: Contribution to journalArticle

Gorden, DL, Myers, DS, Ivanova, PT, Fahy, E, Maurya, MR, Gupta, S, Min, J, Spann, NJ, McDonald, JG, Kelly, SL, Duan, J, Sullards, MC, Leiker, TJ, Barkley, RM, Quehenberger, O, Armando, AM, Milne, SB, Mathews, TP, Armstrong, MD, Li, C, Melvin, WV, Clements, RH, Washington, MK, Mendonsa, AM, Witztum, JL, Guan, Z, Glass, CK, Murphy, RC, Dennis, EA, Merrill, AH, Russell, DW, Subramaniam, S & Brown, HA 2015, 'Biomarkers of NAFLD progression: A lipidomics approach to an epidemic 1', Journal of Lipid Research, vol. 56, no. 3, pp. 722-736. https://doi.org/10.1194/jlr.P056002
Gorden DL, Myers DS, Ivanova PT, Fahy E, Maurya MR, Gupta S et al. Biomarkers of NAFLD progression: A lipidomics approach to an epidemic 1. Journal of Lipid Research. 2015 Mar 1;56(3):722-736. https://doi.org/10.1194/jlr.P056002
Gorden, D. Lee ; Myers, David S. ; Ivanova, Pavlina T. ; Fahy, Eoin ; Maurya, Mano R. ; Gupta, Shakti ; Min, Jun ; Spann, Nathanael J. ; McDonald, Jeffrey G. ; Kelly, Samuel L. ; Duan, Jingjing ; Sullards, M. Cameron ; Leiker, Thomas J. ; Barkley, Robert M. ; Quehenberger, Oswald ; Armando, Aaron M. ; Milne, Stephen B. ; Mathews, Thomas P. ; Armstrong, Michelle D. ; Li, Chijun ; Melvin, Willie V. ; Clements, Ronald H. ; Washington, M. Kay ; Mendonsa, Alisha M. ; Witztum, Joseph L. ; Guan, Ziqiang ; Glass, Christopher K. ; Murphy, Robert C. ; Dennis, Edward A. ; Merrill, Alfred H. ; Russell, David W. ; Subramaniam, Shankar ; Brown, H. Alex. / Biomarkers of NAFLD progression : A lipidomics approach to an epidemic 1. In: Journal of Lipid Research. 2015 ; Vol. 56, No. 3. pp. 722-736.
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AU - Fahy, Eoin

AU - Maurya, Mano R.

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AU - Min, Jun

AU - Spann, Nathanael J.

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AU - Kelly, Samuel L.

AU - Duan, Jingjing

AU - Sullards, M. Cameron

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AU - Barkley, Robert M.

AU - Quehenberger, Oswald

AU - Armando, Aaron M.

AU - Milne, Stephen B.

AU - Mathews, Thomas P.

AU - Armstrong, Michelle D.

AU - Li, Chijun

AU - Melvin, Willie V.

AU - Clements, Ronald H.

AU - Washington, M. Kay

AU - Mendonsa, Alisha M.

AU - Witztum, Joseph L.

AU - Guan, Ziqiang

AU - Glass, Christopher K.

AU - Murphy, Robert C.

AU - Dennis, Edward A.

AU - Merrill, Alfred H.

AU - Russell, David W.

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AU - Brown, H. Alex

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N2 - 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.

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KW - Phospholipids

KW - Sphingolipids

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