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Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of
T S Worgall1, S L Sturley, T Seo
1Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
The Journal of Biological Chemistry
|September 25, 1998
Summary
Unsaturated fatty acids, like oleate, significantly decrease the expression of genes involved in cholesterol and fatty acid metabolism by reducing sterol regulatory element-binding protein (SREBP) levels. Saturated fatty acids showed minimal impact.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Fatty acids and cholesterol are key regulators of membrane physiology, plasma lipid levels, and intracellular sterol homeostasis.
- Sterols influence gene expression via sterol regulatory element-binding protein (SREBP) proteolysis, impacting cholesterol and fatty acid metabolism.
Purpose of the Study:
- To investigate the impact of fatty acids on sterol regulatory element (SRE)-dependent gene expression and SREBP activity.
- To elucidate the mechanisms by which fatty acids modulate lipid metabolism pathways.
Main Methods:
- Utilized three cell lines (HepG2, Chinese hamster ovary, CV-1) transfected with SRE-promoter-luciferase constructs.
- Administered varying concentrations of unsaturated and saturated fatty acids, including oleate.
- Assessed changes in gene transcription, SREBP levels, and HMG-CoA synthase mRNA.
Main Results:
- Micromolar concentrations of unsaturated fatty acids (e.g., oleate, C18:2-C22:6) dose-dependently reduced SRE-regulated gene transcription by 20-75%.
- Saturated fatty acids had minimal effect on SRE-dependent gene expression.
- Oleate decreased mature SREBP-1, SREBP-2, and HMG-CoA synthase mRNA levels, independent of sterol regulation.
Conclusions:
- Unsaturated fatty acids significantly suppress SRE-dependent gene expression, independent of sterol regulation.
- Hypothesize that unsaturated fatty acids may increase intracellular cholesterol pools, thereby affecting mature SREBP levels and downstream gene expression.