Research Papers:

Proteomics and metabolomics analysis of hepatic mitochondrial metabolism in alcohol-preferring and non-preferring rats

Hao-Long Zeng, Qing Yang, Hongying Du, Huijun Li, Ying Shen, Taotao Liu, Xi Chen, Ghulam Mustafa Kamal, Qing Guan, Liming Cheng, Jie Wang _ and Fuqiang Xu

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Oncotarget. 2017; 8:102020-102032. https://doi.org/10.18632/oncotarget.22040

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Hao-Long Zeng1,*, Qing Yang3,*, Hongying Du4, Huijun Li1, Ying Shen1, Taotao Liu1, Xi Chen3, Ghulam Mustafa Kamal6, Qing Guan1, Liming Cheng1, Jie Wang2,5 and Fuqiang Xu2,5,7

1Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China

2State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, P.R. China

3College of Life Sciences, Wuhan University, Wuhan, P.R. China

4Key Laboratory of Environment Correlative Dietology, Ministry of Education, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, P.R. China

5University of Chinese Academy of Sciences, Beijing, P.R. China

6Department of Chemistry, Government College University Faisalabad, Faisalabad, Pakistan

7Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Jie Wang, email: jie.wang@wipm.ac.cn

Fuqiang Xu, email: fuqiang.xu@wipm.ac.cn

Keywords: alcohol preference; liver mitochondria; quantitative proteomics; metabolomics; TCA cycle

Abbreviations: MS: mass spectrometry; NMR: nuclear magnetic resonance; AP: alcohol-preferring; NAP: non-alcohol-preferring

Received: July 18, 2017    Accepted: September 23, 2017    Published: October 25, 2017


Alcohol preference induced tolerance in humans and animals when their bodily functions adapt to compensate for the disruption caused by alcohol consumption. This was thought to be an important component of the genetic predisposition to alcoholism. To investigate the underlying mechanisms of hepatic metabolic tolerance during alcohol preference, the alcohol preferring and alcohol non-preferring rats were used in this study. The liver mitochondria were purified for comparative quantitative proteomics analysis, and the liver metabolite extracts were collected for metabolomics analysis. Our study identified 96 differentially expressed hepatic mitochondrial proteins that associated with alcohol preference, the further gene ontology and protein interaction network analysis suggest a down-regulation of amino acid metabolism and up-regulation of lipid metabolism. We found alcohol preference induced a series of enzymes decreased (e.g. SSADH and GABA-T) and several amino acids increased (e.g. glutamate and aspartate) in rat liver, indicating down-regulations of glutamate degradation occurred during alcohol preference. Most of these changes were due to the genetic differences between alcohol preferring and non-preferring animals. Furthermore, this study would provided new insights to further clarify the mechanisms of hepatic metabolic tolerance during alcohol preference.

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