Serum proteomic analysis of diet-induced steatohepatitis and metabolic syndrome in the Ossabaw miniature swine

Lauren N. Bell, Lydia Lee, Romil Saxena, Kerry G. Bemis, Mu Wang, Janice L. Theodorakis, Raj Vuppalanchi, Mouhamad Alloosh, Michael Sturek, Naga Chalasani

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We recently developed a nutritional model of steatohepatitis and metabolic syndrome in Ossabaw pigs. Here we describe changes in the serum proteome of pigs fed standard chow (control group; n = 7), atherogenic diet (n = 5), or modified atherogenic diet (M-ath diet group; n = 6). Pigs fed atherogenic diet developed metabolic syndrome and mildly abnormal liver histology, whereas pigs fed M-ath diet exhibited severe metabolic syndrome and liver injury closely resembling human nonalcoholic steatohepatitis (NASH). Using a label-free mass spectrometry-based proteomics approach, we identified 1,096 serum proteins, 162 of which changed significantly between any two diet groups (false discovery rate <5%). Biological classification of proteins with significant changes revealed functions previously implicated in development of NASH in humans, including immune system regulation and inflammation (orosomucoid 1, serum amyloid P component, paraoxonase 1, protein similar to α-2-macroglobulin precursor, β-2-microglobulin, p101 protein, and complement components 2 and C8G), lipid metabolism (apolipoproteins C-III, E, E precursor, B, and N), structural and extracellular matrix proteins (transthyretin and endopeptidase 24.16 type M2), and coagulation [carboxypeptidase B2 (plasma)]. Several proteins with significant differential expression in pigs were also identified in our recent human proteomics study as changing significantly in serum from patients across the spectrum of nonalcoholic fatty liver disease, including apolipoproteins C-III and B, orosomucoid 1, serum amyloid P component, transthyretin, paraoxonase 1, and a protein similar to α-2-macroglobulin precursor. This serum proteomic analysis provides additional information about the pathogenesis of NASH and further characterizes our large animal model of diet-induced steatohepatitis and metabolic syndrome in Ossabaw pigs.

Original languageEnglish (US)
Pages (from-to)G746-G754
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume298
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • Animal model
  • Fatty liver disease
  • Fibrosis
  • Mass spectrometry
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

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