title: Biomarkers of NAFLD progression: a lipidomics approach to an epidemic.
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.
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN; Cancer Biology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: D Lee
authors.initials: DL
authors.lastname: Gorden
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: David S
authors.initials: DS
authors.lastname: Myers
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Pavlina T
authors.initials: PT
authors.lastname: Ivanova
authors.affiliation: Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA.
authors.forename: Eoin
authors.initials: E
authors.lastname: Fahy
authors.affiliation: Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA.
authors.forename: Mano R
authors.initials: MR
authors.lastname: Maurya
authors.affiliation: Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA.
authors.forename: Shakti
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Bioengineering, School of Engineering, University of California, San Diego, La Jolla, CA.
authors.forename: Jun
authors.initials: J
authors.lastname: Min
authors.affiliation: Departments of Cellular and Molecular Medicine and Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Nathanael J
authors.initials: NJ
authors.lastname: Spann
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: McDonald
authors.affiliation: Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Kelly
authors.affiliation: Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Duan
authors.affiliation: Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA.
authors.forename: M Cameron
authors.initials: MC
authors.lastname: Sullards
authors.affiliation: Department of Pharmacology, University of Colorado at Denver, Aurora, CO.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Leiker
authors.affiliation: Department of Pharmacology, University of Colorado at Denver, Aurora, CO.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Barkley
authors.affiliation: 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.
authors.forename: Oswald
authors.initials: O
authors.lastname: Quehenberger
authors.affiliation: Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Armando
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Milne
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Mathews
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Armstrong
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC.
authors.forename: Chijun
authors.initials: C
authors.lastname: Li
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Willie V
authors.initials: WV
authors.lastname: Melvin
authors.affiliation: Departments of Surgery, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Clements
authors.affiliation: Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: M Kay
authors.initials: MK
authors.lastname: Washington
authors.affiliation: Cancer Biology, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Alisha M
authors.initials: AM
authors.lastname: Mendonsa
authors.affiliation: Departments of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Department of Biochemistry, Duke University Medical Center, Durham, NC.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Guan
authors.affiliation: Departments of Cellular and Molecular Medicine and Medicine, University of California, San Diego, La Jolla, CA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Glass
authors.affiliation: Department of Pharmacology, University of Colorado at Denver, Aurora, CO.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: 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.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Dennis
authors.affiliation: Schools of Biology, Chemistry, and Biochemistry, and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA.
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: David W
authors.initials: DW
authors.lastname: Russell
authors.affiliation: 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. Electronic address: shankar@ucsd.edu.
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Pharmacology, Vanderbilt University Medical Center, Nashville, TN; Biochemistry, and the Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN. Electronic address: alex.brown@vanderbilt.edu.
authors.forename: H Alex
authors.initials: HA
authors.lastname: Brown
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000453:epidemiology / Q000235:genetics / Q000652:urine; D020641:Polymorphism, Single Nucleotide
chemical_list: D015415:Biomarkers; D008055:Lipids
keywords: diagnostic tools; mass spectrometry; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; phospholipids; sphingolipids