title: Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels.
abstract: BACKGROUND
  Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute pancreatitis. The present study was undertaken to investigate the mitochondrial, sub-mitochondrial and cellular proteomic impact of hypertriglyceridemia in the hepatocytes of hypertriglyceridemic transgenic mice (overexpressing the human apolipoproteinC-III).
  
  
  METHODS
  Quantitative proteomics (2D-DIGE) analysis was carried out on both "low-expressor" (LE) and "high-expressor" (HE) mice, respectively exhibiting moderate and severe HTG, to characterize the effect of the TG plasma level on the proteomic response.
  
  
  RESULTS
  The mitoproteome analysis has revealed a large-scale phenomenon in transgenic mice, i.e. a general down-regulation of matricial proteins and up-regulation of inner membrane proteins. These data also demonstrate that the magnitude of proteomic changes strongly depends on the TG plasma level. Our different analyses indicate that, in HE mice, the capacity of several metabolic pathways is altered to promote the availability of acetyl-CoA, glycerol-3-phosphate, ATP and NADPH for TG de novo biosynthesis. The up-regulation of several cytosolic ROS detoxifying enzymes has also been observed, suggesting that the cytoplasm of HTG mice is subjected to oxidative stress. Moreover, our results suggest that iron over-accumulation takes place in the cytosol of HE mice hepatocytes and may contribute to enhance oxidative stress and to promote cellular proliferation.
  
  
  CONCLUSIONS
  These results indicate that the metabolic response to HTG in human apolipoprotein C-III overexpressing mice may support a high TG production rate and that the cytosol of hepatocytes is subjected to an important oxidative stress, probably as a result of FFA over-accumulation, iron overload and enhanced activity of some ROS-producing catabolic enzymes.
authors.forename: Grégory
authors.initials: G
authors.lastname: Ehx
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gérin
authors.forename: Grégory
authors.initials: G
authors.lastname: Mathy
authors.forename: Fabrice
authors.initials: F
authors.lastname: Franck
authors.forename: Helena Cf
authors.initials: HC
authors.lastname: Oliveira
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.affiliation: Laboratory of Bioenergetics (B22), Department of Life Sciences, University of Liege, Boulevard du rectorat 27, 4000 Liege, Belgium. f.sluse@ulg.ac.be.
authors.forename: Francis E
authors.initials: FE
authors.lastname: Sluse
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics*; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008822:Mice, Transgenic; D008930:Mitochondria, Liver / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*
chemical_list: D053305:Apolipoprotein C-III; D024101:Mitochondrial Proteins; D020543:Proteome