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Analysis of Transcriptome and Metabolome Profiles Alterations in Fatty Liver Induced by High-Fat Diet in Rat

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Wei Jia, Professor and Co-Director of the UNCG Center for Research Excellence in Bioactive Food Components (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

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 ß-oxidation was inhibited and lipogenesis was enhanced. These observations facilitated our understanding of the pathways involved in the development of NAFLD induced by HFD.

Additional Information

Publication
Metabolism: Clinical and Experimental, 59, 554-560
Language: English
Date: 2010
Keywords
fatty liver, nonalcoholic fatty liver disease (NAFLD), diet, rats, rat livers, transcriptome, metabolome profiles