Changes in the hepatic gene expression profile in a rat model of chronic ethanol treatment.
The purpose of this study was to perform a comprehensive analysis of hepatic gene expression in a standard model of an alcohol-induced fatty liver using the cDNA microarray analysis. Male Sprague-Dawley rats were randomly divided into two groups and were given either an ethanol diet (ED), or a control diet (CD) for eight weeks. The ED rats showed significantly elevated levels of plasma total and HDL cholesterol as well as hepatic cholesterol and triglyceride compared to the pair-fed control rats. Among the 5185 genes on the rat cDNA microarray used in the current study, 74 genes were up-regulated and 108 genes were down-regulated greater than 2.0-fold in the liver of ED rats compared with those in the CD rats. The microarray results were verified by conducting real-time RT-PCR on the fourteen selected genes with varied expression ratios. After clustering the regulated genes based on their biological function, it was found that chronic ethanol consumption regulated mainly the genes implicated in the processes of signal transduction, transcription, immune response, and protein/amino acid metabolism. The microarray results obtained in this study revealed, for the first time, that several genes, including beta-glucuronidase, UDP-glycosyltransferase 1, UDP-glucose dehydrogenase, apoC-III, and gonadotropin-releasing hormone receptor, were regulated by chronic ethanol exposure in the rat liver.
Park
Sung-Hee
SH
Department of Food and Nutrition, Brain Korea 21 Project, Yonsei University, 134 Shinchon-dong, Sudaemun-ku, Seoul 120-749, South Korea.
Choi
Myung-Sook
MS
Park
Taesun
T
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000235:genetics; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004032:Diet; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D000596:Amino Acids; D002492:Central Nervous System Depressants; D018076:DNA, Complementary; D008055:Lipids; D000431:Ethanol; D002784:Cholesterol