Analysis of transcriptome and metabolome profiles alterations in fatty liver induced by high-fat diet in rat

Xie, Zuoquan; Li, Houkai; Wang, Ke; Lin, Jingchao; Wang, Qi; Zhao, Guoping; Jia, Wei; Zhang, Qinghua

doi:10.1016/j.metabol.2009.08.022

« Previous Next »Metabolism - Clinical and Experimental
Volume 59, Issue 4 , Pages 554-560, April 2010

Analysis of transcriptome and metabolome profiles alterations in fatty liver induced by high-fat diet in rat

Zuoquan Xie
- State Key laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PRC
- National Engineering Center for Biochip at Shanghai, Shanghai 201203, PRC
- These authors contributed equally to the work.
Houkai Li
- School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, PRC
- These authors contributed equally to the work.
Ke Wang
- National Engineering Center for Biochip at Shanghai, Shanghai 201203, PRC
- Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PRC
Jingchao Lin
- School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, PRC
Qi Wang
- National Engineering Center for Biochip at Shanghai, Shanghai 201203, PRC
Guoping Zhao
- National Engineering Center for Biochip at Shanghai, Shanghai 201203, PRC
Wei Jia
- School of Pharmacy, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, PRC
- Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, NC 28081, USA
- Corresponding authors. Tel.: +86 21 51320297; fax: +86 21 51320266.
Qinghua Zhang
- State Key laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PRC
- National Engineering Center for Biochip at Shanghai, Shanghai 201203, PRC
- Corresponding authors. Tel.: +86 21 51320297; fax: +86 21 51320266.

Received 7 January 2009; accepted 27 August 2009. published online 16 November 2009.

Abstract

Excessive energy intake greatly contributes to the development of nonalcoholic fatty liver disease (NAFLD) in modern society. To better understand the comprehensive mechanisms of NAFLD development, we investigated the metabolic alterations of rats with NAFLD induced by high-fat diet (HFD). Male Wistar rats were fed a HFD or standard chow for control. After 16 weeks, rat serum was collected for biochemical measurement. The rats' livers were resected and subjected to histology inspection and gene expression analysis with complementary DNA microarray and metabolic analysis with gas chromatography–mass spectroscopy. In HFD rats, the serum cholesterol, triglycerides, glucose, and insulin contents were increased; and the total cholesterol and triglycerides in the livers were also significantly increased. Complementary DNA microarray analysis revealed that 130 genes were regulated by HFD. Together with real-time reverse transcriptase polymerase chain reaction, lipid metabolism regulatory members like sterol regulatory element binding factor 1 and stearoyl–coenzyme A desaturase 1 had up-regulation, whereas others like peroxisome proliferator–activated receptor, carnitine palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl–coenzyme A reductase had repressed expression, in HFD rat livers. Metabolomic analysis showed that tetradecanoic acid, hexadecanoic acid, and oleic acid had elevation and arachidonic acid and eicosapentaenoic acid had decreased content in HFD rat livers. Amino acids including glycine, alanine, aspartic acid, glutamic acid, and proline contents were decreased. The integrative results from transcriptomic and metabolomic studies revealed that, in HFD rat livers, fatty acid utilization through β-oxidation was inhibited and lipogenesis was enhanced. These observations facilitated our understanding of the pathways involved in the development of NAFLD induced by HFD.