title: Early changes in the liver-soluble proteome from mice fed a nonalcoholic steatohepatitis inducing diet.
abstract: Despite the increasing incidence of nonalcoholic steatohepatitis (NASH) with the rise in lifestyle-related diseases such as the metabolic syndrome, little is known about the changes in the liver proteome that precede the onset of inflammation and fibrosis. Here, we investigated early changes in the liver-soluble proteome of female C57BL/6N mice fed an NASH-inducing diet by 2D-DIGE and nano-HPLC-MS/MS. In parallel, histology and measurements of hepatic content of triglycerides, cholesterol and intermediates of the methionine cycle were performed. Hepatic steatosis manifested itself after 2 days of feeding, albeit significant changes in the liver-soluble proteome were not evident before day 10 in the absence of inflammatory or fibrotic signs. Proteomic alterations affected mainly energy and amino acid metabolism, detoxification processes, urea cycle, and the one-carbon/S-adenosylmethionine pathways. Additionally, intermediates of relevant affected pathways were quantified from liver tissue, confirming the findings from the proteomic analysis.
authors.affiliation: Institute of Functional Genomics, University of Regensburg, Josef-Engert-Strasse 9, Regensburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Thomas
authors.forename: Axel P
authors.initials: AP
authors.lastname: Stevens
authors.forename: Matthias S
authors.initials: MS
authors.lastname: Klein
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Katja
authors.initials: K
authors.lastname: Dettmer
authors.forename: Wolfram
authors.initials: W
authors.lastname: Gronwald
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Oefner
authors.forename: Jörg
authors.initials: J
authors.lastname: Reinders
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D004032:Diet; D015180:Electrophoresis, Gel, Two-Dimensional; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005990:Glycerol / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D055432:Metabolomics; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D020543:Proteome / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D040901:Proteomics; D015203:Reproducibility of Results; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D020543:Proteome; D012436:S-Adenosylmethionine; D002784:Cholesterol; D005990:Glycerol