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Lipids and Membrane Proteins that Regulate Genes of Lipid Metabolism
Author(s) -
Jump Donald B.,
Wang Yun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.251.2
Subject(s) - lipid metabolism , biochemistry , sterol regulatory element binding protein , fatty acid , fatty acid metabolism , peroxisome , metabolic pathway , peroxisome proliferator activated receptor , metabolism , enzyme , biology , chemistry , gene , gene expression
The liver plays a central role in whole body lipid metabolism and responds rapidly to changes in dietary fat composition. Fatty acid effects on hepatic lipid metabolism are mediated, at least in part, through three transcriptional regulatory networks: PPARα, SREBP1 and ChREBP/MLX. Changes in PPARα activity and expression of its target genes correlate well with changes in intracellular non‐esterified fatty acids. Ligand activation studies, however, suggest that fatty acid structure affects PPARα activity. One metabolic pathway was identified as potentially affecting PPARα activity, i.e., fatty acid elongation. Fatty acid elongases are ER‐associated enzymes. An adenoviral‐mediated approach was used to over express the fatty acid elongase, Elovl5, in mouse liver. Elevated Elovl5 enzyme activity promoted changes in both hepatic and blood lipid composition. Elevated Elovl5 activity also attenuated expression of several PPARα‐regulated genes without significant effects on SREBP1‐ or ChREBP/MLX‐regulated genes. Amongst the 4 elongase subtypes expressed in liver, Elovl5 is abundant and well‐regulated. These studies suggest that metabolic pathways affecting fatty acid structure may play a role in controlling PPARα function. Supported by NIH DK43220.