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| http://dx.doi.org/10.1155/2009/589626 | DOI Listing |
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Tuning RXR Modulators for PGC1α Recruitment.
J Med Chem
September 2024
Department of Pharmacy, Ludwig-Maximilians-Universität (LMU) München, 81377 Munich, Germany.
Article Synopsis
- The activation of nuclear retinoid X receptors (RXRs) involves releasing corepressors and recruiting coactivators, influencing gene activation or repression.
- Research identified a synthetic agonist that significantly increases the binding of PGC1α (a coactivator) to RXR, unlike the natural ligand 9-cis retinoic acid.
- The study produced three related RXR agonists with varying abilities to enhance PGC1α recruitment, suggesting potential new therapies through targeted RXR-PGC1α interactions via selective coregulator modulation.
Different Coactivator Recruitment to Human PPARα/δ/γ Ligand-Binding Domains by Eight PPAR Agonists to Treat Nonalcoholic Fatty Liver Disease.
Biomedicines
March 2024
Department of Health Chemistry, Showa Pharmaceutical University, Machida 194-8543, Tokyo, Japan.
Article Synopsis
- The text discusses three types of peroxisome proliferator-activated receptors (PPARs) - PPARα, PPAR(ß/)δ, and PPARγ - and their role in gene transcription regulation through interactions with retinoid X receptors (RXRs)
- It highlights how ligand-bound PPAR/RXR complexes recruit specific coactivator proteins to gene regulatory locations, impacting gene expression, but emphasizes that each PPAR can interact with only one coactivator at a time via a specific motif (LXXLL)
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Naringenin and β-carotene convert human white adipocytes to a beige phenotype and elevate hormone- stimulated lipolysis.
Front Endocrinol (Lausanne)
May 2023
Nutrition and Chronic Disease, Pennington Biomedical Research Center, Baton Rouge, LA, United States.
Introduction: Naringenin, a peroxisome proliferator-activated receptor (PPAR) activator found in citrus fruits, upregulates markers of thermogenesis and insulin sensitivity in human adipose tissue. Our pharmacokinetics clinical trial demonstrated that naringenin is safe and bioavailable, and our case report showed that naringenin causes weight loss and improves insulin sensitivity. PPARs form heterodimers with retinoic-X-receptors (RXRs) at promoter elements of target genes.
View Article and Find Full Text PDF2,4-Di-tert-butylphenol Induces Adipogenesis in Human Mesenchymal Stem Cells by Activating Retinoid X Receptors.
Endocrinology
February 2023
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-2300, USA.
2,4-Di-tert-butylphenol (2,4-DTBP) is an important commercial antioxidant and a toxic natural secondary metabolite that has been detected in humans. However, there is scant information regarding its toxicological effects. We asked whether 2,4-DTBP is a potential obesogen.
View Article and Find Full Text PDFRetinoid X Receptor: Cellular and Biochemical Roles of Nuclear Receptor with a Focus on Neuropathological Involvement.
Mol Neurobiol
April 2022
Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
Retinoid X receptors (RXRs) present a subgroup of the nuclear receptor superfamily with particularly high evolutionary conservation of ligand binding domain. The receptor exists in α, β, and γ isotypes that form homo-/heterodimeric complexes with other permissive and non-permissive receptors. While research has identified the biochemical roles of several nuclear receptor family members, the roles of RXRs in various neurological disorders remain relatively under-investigated.
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