The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Cross-Talk between Peroxisome Proliferator-Activated Receptor (PPAR) α and Liver X Receptor (LXR) in Nutritional Regulation of Fatty Acid Metabolism. I. PPARs Suppress Sterol Regulatory Element Binding Protein-1c Promoter through Inhibition of LXR Signaling
Abstract
Liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors that form obligate heterodimers with retinoid X receptors (RXRs). These nuclear receptors play crucial roles in the regulation of fatty acid metabolism: LXRs activate expression of sterol regulatory element-binding protein 1c (SREBP-1c), a dominant lipogenic gene regulator, whereas PPARalpha promotes fatty acid beta-oxidation genes. In the current study, effects of PPARs on the LXR-SREBP-1c pathway were investigated. Luciferase assays in human embryonic kidney 293 cells showed that overexpression of PPARalpha and gamma dose-dependently inhibited SREBP-1c promoter activity induced by LXR. Deletion and mutation studies demonstrated that the two LXR response elements (LXREs) in the SREBP-1c promoter region are responsible for this inhibitory effect of PPARs. Gel shift assays indicated that PPARs reduce binding of LXR/RXR to LXRE. PPARalpha-selective agonist enhanced these inhibitory effects. Supplementation with RXR attenuated these inhibitions by PPARs in luciferase and gel shift assays, implicating receptor interaction among LXR, PPAR, and RXR as a plausible mechanism. Competition of PPARalpha ligand with LXR ligand was observed in LXR/RXR binding to LXRE in gel shift assay, in LXR/RXR formation in nuclear extracts by coimmunoprecipitation, and in gene expression of SREBP-1c by Northern blot analysis of rat primary hepatocytes and mouse liver RNA. These data suggest that PPARalpha activation can suppress LXR-SREBP-1c pathway through reduction of LXR/RXR formation, proposing a novel transcription factor cross-talk between LXR and PPARalpha in hepatic lipid homeostasis.
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The Opposing Effects of N-3 and n-6 Fatty Acids
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Peroxisome Proliferator-Activated Receptor Alpha Target Genes
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Molecular Actions of PPARα in Lipid Metabolism and Inflammation
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Essential fatty acids as functional components of foods- a review
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Metadata
- Authors
- Yoshikawa, T., Ide, T., Shimano, H., Yahagi, N., Amemiya-Kudo, M., Matsuzaka, T., Yatoh, S., Kitamine, T., Okazaki, H., Tamura, Y., Sekiya, M., Takahashi, A., Hasty, A. H., Sato, R., Sone, H., Osuga, J.-I., Ishibashi, S., & Yamada, N.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2003-07
- Volume
- 17
- Issue
- 7
- Pages
- 1240-1254
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2017918116
- Cited by
- 297
- References
- 10
- FWCI
- 5.25
- Type
- journal article
- Language
- en
- Open access
- closed
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