Journal of Lipid Research (Mar 2015)
Biomarkers of NAFLD progression: a lipidomics approach to an epidemic1[S]
- 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 Li,
- Willie 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, Jr.,
- David W. Russell,
- Shankar Subramaniam,
- H.Alex Brown
Affiliations
- D.Lee Gorden
- Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN; Cancer Biology, Vanderbilt University Medical Center, Nashville, TN
- David S. Myers
- Pharmacology, Vanderbilt University Medical Center, Nashville, TN
- Pavlina T. Ivanova
- Pharmacology, Vanderbilt University Medical Center, Nashville, TN
- Eoin Fahy
- Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA
- Mano R. Maurya
- Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA
- Shakti Gupta
- Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA
- Jun Min
- Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA
- Nathanael J. Spann
- Departments of Cellular and Molecular Medicine and Medicine, University of California, San Diego, La Jolla, CA
- Jeffrey G. McDonald
- Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX
- Samuel L. Kelly
- Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- Jingjing Duan
- Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- M.Cameron Sullards
- Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- Thomas J. Leiker
- Department of Pharmacology, University of Colorado at Denver, Aurora, CO
- Robert M. Barkley
- Department of Pharmacology, University of Colorado at Denver, Aurora, CO
- Oswald Quehenberger
- Departments of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA; Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA
- Aaron M. Armando
- Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA
- Stephen B. Milne
- Pharmacology, Vanderbilt University Medical Center, Nashville, TN
- Thomas P. Mathews
- Pharmacology, Vanderbilt University Medical Center, Nashville, TN
- Michelle D. Armstrong
- Pharmacology, Vanderbilt University Medical Center, Nashville, TN
- Chijun Li
- Department of Biochemistry, Duke University Medical Center, Durham, NC
- Willie V. Melvin
- Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN
- Ronald H. Clements
- Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN
- M.Kay Washington
- Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN
- Alisha M. Mendonsa
- Cancer Biology, Vanderbilt University Medical Center, Nashville, TN
- Joseph L. Witztum
- Departments of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA
- Ziqiang Guan
- Department of Biochemistry, Duke University Medical Center, Durham, NC
- Christopher K. Glass
- Departments of Cellular and Molecular Medicine and Medicine, University of California, San Diego, La Jolla, CA
- Robert C. Murphy
- Department of Pharmacology, University of Colorado at Denver, Aurora, CO
- Edward A. Dennis
- Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA; Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, CA
- Alfred H. Merrill, Jr.
- Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA
- David W. Russell
- Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX
- Shankar Subramaniam
- To whom correspondence should be addressed. (H.A.B.); (S.S.); Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA; Chemistry and Biochemistry, School of Medicine, University of California, San Diego, La Jolla, CA
- H.Alex Brown
- To whom correspondence should be addressed. (H.A.B.); (S.S.); Pharmacology, Vanderbilt University Medical Center, Nashville, TN; Biochemistry, and the Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN
- Journal volume & issue
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Vol. 56,
no. 3
pp. 722 – 736
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.
