DNA microarray analysis identified molecular pathways mediating the effects of supplementation of branched-chain amino acids on CCl4-induced cirrhosis in rats
Version of Record online: 20 NOV 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 57, Issue 2, pages 291–306, February 2013
How to Cite
Jia, H., Takahashi, S., Saito, K. and Kato, H. (2013), DNA microarray analysis identified molecular pathways mediating the effects of supplementation of branched-chain amino acids on CCl4-induced cirrhosis in rats. Mol. Nutr. Food Res., 57: 291–306. doi: 10.1002/mnfr.201200538
- Issue online: 22 JAN 2013
- Version of Record online: 20 NOV 2012
- Manuscript Accepted: 26 SEP 2012
- Manuscript Revised: 13 SEP 2012
- Manuscript Received: 12 AUG 2012
- DNA microarray;
- Liver cirrhosis;
- Nutritional status;
- Skeletal muscle
This study addresses the effects of branched-chain amino acids (BCAA) on global gene expression in liver and skeletal muscle and the molecular mechanisms underlying the improvement in liver cirrhosis using DNA microarray analysis combined with RNase protection assay.
Methods and results
Male Wistar rats administered carbon tetrachloride (CCl4) repeatedly for 19 weeks as a decompensated cirrhosis model were thereafter given BCAA-enriched diet (AL) or normal diet (LC) for 5 weeks. The control-diet rats without CCl4 administration were used as a normal control group. Gene expression in AL was reversed by twofold greater than in LC in the microarray were selected to elucidate the improvements in nutritional and metabolic disorders. Downregulation of fatty acid translocase (FAT)/Cd36, glutamine synthetase, and pyruvate dehydrogenase kinase isoenzyme 4 is believed to promote lower uptake of fatty acids, lower ammonia incorporation, and higher uptake of glucose, and thus to provide an energy source without using BCAA. Ultimately, the catabolism of BCAA and skeletal muscle protein would be slowed, maintaining BCAA concentrations in blood.
We established, for the first time, the regulatory gene pathways of processes involved in hepatic fibrosis and energy metabolism (hypoalbuminemia, hyperammonemia, and carbohydrate catabolism, and their relationships) under BCAA supplementation.