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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 KC, Zannis VI - Pharmacogenomics J. (2009)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens.

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 beta-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.

Show MeSH
Pathways of lipid and lipoprotein metabolism affected by fenofibrate. Upregulation of genes involved in phospholipid biosynthesis, HDL synthesis and remodeling. Upregulation of genes involved in lipolysis, FA transport, β-oxidation, synthesis of unsaturated fatty acids and long-chain fatty acids.
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fig3: Pathways of lipid and lipoprotein metabolism affected by fenofibrate. Upregulation of genes involved in phospholipid biosynthesis, HDL synthesis and remodeling. Upregulation of genes involved in lipolysis, FA transport, β-oxidation, synthesis of unsaturated fatty acids and long-chain fatty acids.

Mentions: The genes encoding the lipolytic enzymes Lpl and pancreatic lipase-related protein 1 (Pnliprp1) were upregulated 8.85- and 19.06-fold, respectively, whereas Apoa5 that promotes lipolysis37 did not change (Figure 3, Table 1 and Supplementary Table 2).


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 KC, Zannis VI - Pharmacogenomics J. (2009)

Pathways of lipid and lipoprotein metabolism affected by fenofibrate. Upregulation of genes involved in phospholipid biosynthesis, HDL synthesis and remodeling. Upregulation of genes involved in lipolysis, FA transport, β-oxidation, synthesis of unsaturated fatty acids and long-chain fatty acids.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875298&req=5

fig3: Pathways of lipid and lipoprotein metabolism affected by fenofibrate. Upregulation of genes involved in phospholipid biosynthesis, HDL synthesis and remodeling. Upregulation of genes involved in lipolysis, FA transport, β-oxidation, synthesis of unsaturated fatty acids and long-chain fatty acids.
Mentions: The genes encoding the lipolytic enzymes Lpl and pancreatic lipase-related protein 1 (Pnliprp1) were upregulated 8.85- and 19.06-fold, respectively, whereas Apoa5 that promotes lipolysis37 did not change (Figure 3, Table 1 and Supplementary Table 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens.

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 beta-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.

Show MeSH