We have used a new apoA-1 transgenic mouse model in order to identify by global gene expression profiling, candidate genes that affect plasma lipids and HDL following fenofibrate treatment. Multi-level bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate treated group did not have significantly altered levels of hepatic human APOA1 mRNA and plasma apoA-I as compared to the untreated group. However, the treated group had significantly increased cholesterol levels mainly due to increased HDL. The observed changes in HDL are associated with the upregulation of several genes involved in phospholipid biosynthesis. Consistent with previous studies, significant upregulation was observed in genes involved in lipid hydrolysis, fatty acid transport, β-oxidation and phospholipid transfer protein but not in fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and HDL metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.
|Number of pages||3|
|Journal||Epitheorese Klinikes Farmakologias kai Farmakokinetikes|
|Publication status||Published - 27 May 2009|
- Lipids metabolism
ASJC Scopus subject areas
- Pharmacology (medical)