title: Molecular classification of fatty liver by high-throughput profiling of protein post-translational modifications.
abstract: We describe an alternative approach to classifying fatty liver by profiling protein post-translational modifications (PTMs) with high-throughput capillary isoelectric focusing (cIEF) immunoassays. Four strains of mice were studied, with fatty livers induced by different causes, such as ageing, genetic mutation, acute drug usage, and high-fat diet. Nutrient-sensitive PTMs of a panel of 12 liver metabolic and signalling proteins were simultaneously evaluated with cIEF immunoassays, using nanograms of total cellular protein per assay. Changes to liver protein acetylation, phosphorylation, and O-N-acetylglucosamine glycosylation were quantified and compared between normal and diseased states. Fatty liver tissues could be distinguished from one another by distinctive protein PTM profiles. Fatty liver is currently classified by morphological assessment of lipid droplets, without identifying the underlying molecular causes. In contrast, high-throughput profiling of protein PTMs has the potential to provide molecular classification of fatty liver.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, NV, USA.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Urasaki
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, NV, USA.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Fiscus
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Roseman University of Health Sciences, 10530 Discovery Drive, Las Vegas, NV, USA.
authors.forename: Thuc T
authors.initials: TT
authors.lastname: Le
mesh_terms: D000107:Acetylation; D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000145:classification / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006031:Glycosylation; D057166:High-Throughput Screening Assays; D007118:Immunoassay; D007525:Isoelectric Focusing; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D011506:Proteins
keywords: capillary isoelectric focusing immunoassay; coherent anti-Stokes Raman scattering microscopy; fatty liver disease; liver energy metabolism; molecular classification; nutrient sensing