GENE EXPRESSION PROFILING OF RAT LIVER TREATED WITH SERUM TRIGLYCERIDE-DECREASING COMPOUNDS

• Published in: Journal of toxicological sciences 2007, Vol.32(4), pp.387-399
• Main Authors: OMURA, Ko, KIYOSAWA, Naoki, UEHARA, Takeki, HIRODE, Mitsuhiro, SHIMIZU, Toshinobu, MIYAGISHIMA, Toshikazu, ONO, Atsushi, NAGAO, Taku, URUSHIDANI, Tetsuro
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers, Pharmacological - analysis; Biomarkers, Pharmacological - blood; Databases, Genetic; Drug-Related Side Effects and Adverse Reactions; Gene Expression - drug effects; Gene Expression Profiling; Liver - drug effects; Liver - metabolism; Male; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Rats; Rats, Inbred Strains; Triglycerides - blood
• ISSN: 0388-1350; 1880-3989
• DOI: 10.2131/jts.32.387

We have constructed a large-scale transcriptome database of rat liver treated with various drugs. In an effort to identify a biomarker for interpretation of plasma triglyceride (TG) decrease, we extracted 218 probe sets of rat hepatic genes from data of 15 drugs that decreased the plasma TG level but differentially affected food consumption. Pathway and gene ontology analysis revealed that the genes belong to amino acid metabolism, lipid metabolism and xenobiotics metabolism. Principal component analysis (PCA) showed that 12 out of 15 compounds were separated in the direction of PC1, and these 12 were separated in the direction of PC2, according to their hepatic gene expression profiles. It was found that genes with either large or small eigenvector values in principal component PC 2 were those reported to be regulated by peroxisome proliferator-activated receptor (PPAR)α or constitutive androstane receptor (CAR), respectively. In fact, WY-14,643, clofibrate, gemfibrozil and benzbromarone, reported to be PPARα activators, distributed to the former, whereas propylthiouracil, omeprazole, phenobarbital, thioacetamide, methapyrilene, sulfasalazine and coumarin did to the latter. We conclude that these identified 218 probe sets could be a useful source of biomarkers for classification of plasma TG decrease, based on the mechanisms involving PPARα and CAR.