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. Biomarkers of NAFLD progression : a lipidomics approach to an epidemic. Journal of lipid research. 2015 Jan 17. PMID: 25598080 [PubMed]
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, single nucleotide polymorphisms (SNP), 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 (LDA), 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.