Liver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels

Lipids in Health and Disease

Research

Helena C F Oliveira¹  Anibal E Vercesi²  Fabrice Franck³  Grégory Mathy³  Francis E Sluse³  Grégory Ehx³  Stéphanie Gérin³ 

[1] Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-887, Campinas, SP, Brazil;Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), CEP: 13083-887, Campinas, São Paulo, Brazil;Laboratory of Bioenergetics (B22), Department of Life Sciences, University of Liege, Boulevard du rectorat 27, 4000, Liege, Belgium;

关键词: NASH;    Protein Spot;    Urea Cycle;    mitoKATP Channel;    Hepatic Iron Overload;   

DOI  :  10.1186/1476-511X-13-116

 received in 2014-03-20, accepted in 2014-07-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundHypertriglyceridemia (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).MethodsQuantitative 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.ResultsThe 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.ConclusionsThese 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.

【 授权许可】

Unknown   
© Ehx et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.