Biomarkers of NAFLD progression: a lipidomics approach to an epidemic

• DOI: 10.1194/jlr.p056002
• Publication Date: 2015-01-18T03:07:59Z
• Authors: 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. Armst...; 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; David W. Russell; Shankar Subramaniam; H.Alex Brown
• Keywords: Adult; Male; 0303 health sciences; Middle Aged; Lipids; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Double-Blind Method; Non-alcoholic Fatty Liver Disease; Humans; Female; Biomarkers

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.