title: DNA microarray analysis identified molecular pathways mediating the effects of supplementation of branched-chain amino acids on CCl4-induced cirrhosis in rats.
abstract: METHODS
  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.
  
  
  RESULTS
  Male Wistar rats administered carbon tetrachloride (CCl(4) ) 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 CCl(4)  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Corporate Sponsored Research Program Food for Life, Organization for Interdisciplinary Research Projects, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Jia
authors.forename: Shoko
authors.initials: S
authors.lastname: Takahashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Saito
authors.forename: Hisanori
authors.initials: H
authors.lastname: Kato
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000008:administration & dosage* / Q000097:blood; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D019587:Dietary Supplements; D015536:Down-Regulation; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D022124:Hyperammonemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D000597:Amino Acids, Branched-Chain; D018955:CD36 Antigens; C000631440:Pdk4 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D002251:Carbon Tetrachloride; D017346:Protein Serine-Threonine Kinases; D005974:Glutamate-Ammonia Ligase