Cross-Talk between Fatty Acid and Cholesterol Metabolism Mediated by Liver X Receptor-α
| Autor: | Hilde I. Nebb, Kari Anne Risan Tobin, Øystein Spydevold, Hilde Hermansen Steineger, Jan-Åke Gustafsson, Johan Auwerx, Siegfried Alberti |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
Transcription Genetic Receptors Retinoic Acid Receptors Cytoplasmic and Nuclear Regulatory Sequences Nucleic Acid Mice chemistry.chemical_compound Liver Neoplasms Experimental Endocrinology Genes Reporter Tumor Cells Cultured Luciferases Cells Cultured Liver X Receptors chemistry.chemical_classification Receptors Thyroid Hormone Fatty Acids alpha-Linolenic Acid Liver X receptor alpha Tetradecylthioacetic acid Fasting General Medicine Orphan Nuclear Receptors Neoplasm Proteins DNA-Binding Proteins Cholesterol Liver Biochemistry Fatty acid analog Fatty Acids Unsaturated Free fatty acid receptor Peroxisome Proliferators lipids (amino acids peptides and proteins) Half-Life Signal Transduction Recombinant Fusion Proteins Sulfides Biology Transfection Free fatty acid receptor 1 Animals Humans RNA Messenger Rats Wistar adipocyte protein 2 Liver X receptor Molecular Biology Fatty acid Receptor Cross-Talk Dietary Fats Rats Pyrimidines Gene Expression Regulation chemistry biology.protein |
| Zdroj: | Molecular Endocrinology. 14:741-752 |
| ISSN: | 1944-9917 0888-8809 |
| DOI: | 10.1210/mend.14.5.0459 |
| Popis: | LXR alpha (liver X receptor, also called RLD-1) is a nuclear receptor, highly expressed in tissues that play a role in lipid homeostasis. In this report we show that fatty acids are positive regulators of LXR alpha gene expression and we investigate the molecular mechanisms underlying this regulation. In cultured rat hepatoma and primary hepatocyte cells, fatty acids and the sulfur-substituted fatty acid analog, tetradecylthioacetic acid, robustly induce LXR alpha (up to 3.5- and 7-fold, respectively) but not LXR beta (also called OR-1) mRNA steady state levels, with unsaturated fatty acids being more effective than saturated fatty acids. RNA stability and nuclear run-on studies demonstrate that changes in the transcription rate of the LXR alpha gene account for the major part of the induction of LXR alpha mRNA levels. A similar induction of protein level was also seen after treatment of primary hepatocytes with the same fatty acids. Consistent with such a transcriptional effect, transient transfection studies with a luciferase reporter gene, driven by 1.5 kb of the 5'-flanking region of the mouse (m)LXR alpha gene, show a peroxisome proliferator-activated receptor-alpha-dependent increase in luciferase activity upon treatment with tetradecylthioacetic acid and the synthetic peroxisome proliferator-activated receptor-alpha activator, Wy 14.643, suggesting that the mLXR alpha 5'-flanking region contains the necessary sequence elements for fatty acid responsiveness. In addition, in vivo LXR alpha expression was induced by fatty acids, consistent with the in vitro cell culture data. These observations demonstrate that LXR alpha expression is controlled by fatty acid signaling pathways and suggest an important cross-talk between fatty acid and cholesterol regulation of lipid metabolism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|