TABLE 3.
HEPATIC GENE EXPRESSION MODULATIONS INDUCED BY FENOFIBRATE OR LGD1069 IN WILD-TYPE AND PPARα −/− MICE
| Genes | Wild-Type | PPARα −/− | CT PPARα −/−/wt | Function | ||
|---|---|---|---|---|---|---|
| Feno/CT | LGD1069/CT | Feno/CT | LGD1069/CT | |||
| Cyp4al0 | 32.9† | 7.8† | ns | ns | ns | microsomal FA ω-hydroxylation |
| Cyp4al4 | 44.8† | 12.0† | ns | ns | 2.4† | microsomal FA ω-hydroxylation |
| AOX | 6.4† | 2.5† | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| BIEN | 40.0† | 5.1† | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| THIOL | 8.5† | 3.8† | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| PECI | 2.1† | ns | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| PMDCI | 3.2† | ns | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| Pex11a | 2.1† | ns | ns | ns | ns | peroxisomal FA oxidation and biogenesis |
| CACP | 1.8† | ns | ns | ns | ns | mitochondrial FA oxidation and energy homeostasis |
| CPT2 | 1.7† | ns | ns | ns | ns | mitochondrial FA oxidation and energy homeostasis |
| MCAD | 2.8† | ns | ns | Ns | 1.6* | mitochondrial FA oxidation and energy homeostasis |
| Tpα | 2.4† | ns | ns | ns | ns | mitochondrial FA oxidation and energy homeostasis |
| mHMGCoAS | 3.1† | 1.5* | ns | ns | ns | mitochondrial FA oxidation and energy homeostasis |
| PDK4 | 3.3† | ns | ns | ns | ns | mitochondrial FA oxidation and energy homeostasis |
| ACOTH | 6.3† | 2.0* | ns | ns | ns | FA metabolism |
| FAT/CD36 | 1.91† | ns | ns | ns | ns | FA transport |
| L-FABP | 4.2† | ns | ns | ns | ns | FA trafficking |
| FAS | ns | 3.5† | ns | 2.4† | ns | lipogenesis |
| S14 | ns | 2.4† | ns | ns | Ns | lipogenesis |
| Cyp26 | ns | 3.5† | ns | 4.4† | ns | other cytochromes P450 |
| Cyp2bl0 | ns | 4.6† | 1.7† | 3.3† | ns | other cytochromes P450 |
| Cyp2c29 | −1.6† | 2.2† | ns | 1.7† | 1.5† | other cytochromes P450 |
| Cyp8bl | 1.8* | −2.1† | ns | ns | ns | other cytochromes P450 |
| ALDH3 | 4.1† | ns | ns | ns | ns | fatty aldehyde dehydrogenase |
| GSTμ | ns | 2.2† | ns | ns | ns | glutathione S-transferases |
| GSTπ2 | ns | −3.6† | ns | ns | −2.9† | glutathione S-transferases |
| LCE | −1.6† | ns | ns | ns | ns | TG hydrolysis |
| PLTP | 2.0† | ns | ns | ns | ns | lipoprotein metabolism |
| apoC-III | ns | ns | ns | ns | 1.6† | lipoprotein metabolism |
| PPARα | 1.6† | ns | ns | ns | ns | nuclear receptor |
| SPI1 | −2.7† | −2.1† | ns | −1.6* | −1.6* | acute phase response |
| ADISP/FSP27 | 2.0† | ns | ns | ns | ns | apoptosis |
| BSEP | ns | ns | ns | 1.9† | ns | bile salt transport |
Hepatic total RNA from wild-type and PPARα −/− mice treated with fenofibrate (Feno), LGD1069, or vehicle alone (CT) were hybridized to INRArray 01.2 (n = 3 or 4 per group, total of 22 macroarrays). Raw data were normalized by the mean log(signal) of eight artificial mRNAs spiked into the samples. Normalized data were subjected to an ANOVA followed by a two-tailed Student’s test using a Bonferroni comparison-wise error rate protection. The ratios (fold change) of transcript abundance correspond to the comparisons between the groups indicated in the headings of the columns. Genes presented exhibited at least one highly significant (p < 0.002) gene expression modulation of 1.5-fold amplitude minimum out of the five comparisons studied. wt: wild-type.
Due to the Bonferroni p-value adjustments: *raw p <0.01 and †raw p < 0.002. ns: a nonsignificant expression ratio (raw p > 0.01).