Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice

D. Sanoudou, A. Duka, K. Drosatos, K. C. Hayes, V. I. Zannis

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel 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 APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and Β-oxidation, but not in those of 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 lipoprotein 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.

Original languageEnglish
Pages (from-to)165-179
Number of pages15
JournalPharmacogenomics Journal
Volume10
Issue number3
DOIs
Publication statusPublished - 1 Jun 2010
Externally publishedYes

Fingerprint

Fibric Acids
Apolipoprotein A-I
Lipid Metabolism
Transgenic Mice
Fenofibrate
Genes
Lipoproteins
Up-Regulation
Fatty Acids
Cholesterol
Phospholipid Transfer Proteins
Multilevel Analysis
Citric Acid Cycle
Gluconeogenesis
Gene Expression Profiling
HDL Lipoproteins
Patient Selection
HDL Cholesterol
Phospholipids
Hydrolysis

Keywords

  • Estrogen receptor-related gamma HDL
  • Fenofibrate
  • Lipid catabolism
  • Phospholipid biosynthesis

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics

Cite this

Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice. / Sanoudou, D.; Duka, A.; Drosatos, K.; Hayes, K. C.; Zannis, V. I.

In: Pharmacogenomics Journal, Vol. 10, No. 3, 01.06.2010, p. 165-179.

Research output: Contribution to journalArticle

Sanoudou, D. ; Duka, A. ; Drosatos, K. ; Hayes, K. C. ; Zannis, V. I. / Role of Esrrg in the fibrate-mediated regulation of lipid metabolism genes in human ApoA-I transgenic mice. In: Pharmacogenomics Journal. 2010 ; Vol. 10, No. 3. pp. 165-179.
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