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Early changes in the liver‐soluble proteome from mice fed a nonalcoholic steatohepatitis inducing diet
Author(s) -
Thomas Anja,
Stevens Axel P.,
Klein Matthias S.,
Hellerbrand Claus,
Dettmer Katja,
Gronwald Wolfram,
Oefner Peter J.,
Reinders Jörg
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100628
Subject(s) - proteome , nonalcoholic steatohepatitis , methionine , steatosis , biology , steatohepatitis , urea cycle , endocrinology , medicine , metabolism , biochemistry , nonalcoholic fatty liver disease , fatty liver , amino acid , disease , arginine
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 C 57 BL /6 N 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.