ArticleNuclear receptor signaling2015
Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal anti-inflammatory drugs.
Article in Nuclear receptor signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Cheminformatics-based read-across prioritization of food additives with obesogenic potential and PPARγ agonist activity.Archives of toxicology · 2026Article
- Select NSAIDs enhance peripheral nerve growth and calcium signaling through PPARγ activation.Molecular and cellular neurosciences · 2026Article
- Glial Cell Dynamics in Neuroinflammation: Mechanisms, Interactions, and Therapeutic Implications.Biomedicines · 2026Review
- Targeting Tris(2,3-dibromopropyl) Isocyanurate-Induced Inflammation in Hippocampal Neurons In Vitro: Mechanistic Insights and Implications for Neurodegenerative Disease Prevention.Molecular neurobiology · 2025Article
- Prostaglandin E2 inhibits adipogenesis through the cilia-dependent activation of ROCK2.Journal of cell science · 2025Article
- Neuroinflammation: Mechanisms, Dual Roles, and Therapeutic Strategies in Neurological Disorders.Current issues in molecular biology · 2025Review
- Medication Exposure and Risk of Dementia and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Regulated adipose tissue-specific expression of humaniScience · 2023Article
- Poor Adherence to Self-Applied Topical Drug Treatment Is a Common Source of Low Lesion Clearance in Patients with Actinic Keratosis-A Cross-Sectional Study.Journal of clinical medicine · 2023Article
- Anti-Obesity and Anti-Inflammatory Effects of Novel Carvacrol Derivatives on 3T3-L1 and WJ-MSCs Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Horse serum potentiates cellular viability and improves indomethacin-induced adipogenesis in equine subcutaneous adipose-derived stem cells (ASCs).International journal of veterinary science and medicine · 2023Article
- Article
- Review
- The Role of Transcription Factor PPAR-γ in the Pathogenesis of Psoriasis, Skin Cells, and Immune Cells.International journal of molecular sciences · 2022Review
- NSAIDs Induce Proline Dehydrogenase/Proline Oxidase-Dependent and Independent Apoptosis in MCF7 Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Nonsteroidal Anti-Inflammatory Drugs as PPARγ Agonists Can Induce PRODH/POX-Dependent Apoptosis in Breast Cancer Cells: New Alternative Pathway in NSAID-Induced Apoptosis.International journal of molecular sciences · 2022Article
- Repurposing Small Molecules to Target PPAR-γ as New Therapies for Peripheral Nerve Injuries.Biomolecules · 2021Review
- Drug-induced hepatic steatosis in absence of severe mitochondrial dysfunction in HepaRG cells: proof of multiple mechanism-based toxicity.Cell biology and toxicology · 2021Article
- A Comparison of the Antinociceptive Properties of SJP-005 and Morphine in Rats.Pharmaceutics · 2021Article
- A Small Fraction of Progenitors Differentiate Into Mature Adipocytes by Escaping the Constraints on the Cell Structure.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) display anti-inflammatory, antipyretic and analgesic properties by inhibiting cyclooxygenases and blocking prostaglandin production. Previous studies, however, suggested that some NSAIDs also modulate peroxisome proliferator activated receptors (PPARs), raising the possibility that such off target effects contribute to the spectrum of clinically relevant NSAID actions. In this study, we set out to understand how peroxisome proliferator activated receptor-γ (PPARγ/PPARG) interacts with NSAIDs using X-ray crystallography and to relate ligand binding modes to effects on receptor activity. We find that several NSAIDs (sulindac sulfide, diclofenac, indomethacin and ibuprofen) bind PPARγ and modulate PPARγ activity at pharmacologically relevant concentrations. Diclofenac acts as a partial agonist and binds to the PPARγ ligand binding pocket (LBP) in typical partial agonist mode, near the β-sheets and helix 3. By contrast, two copies of indomethacin and sulindac sulfide bind the LBP and, in aggregate, these ligands engage in LBP contacts that resemble agonists. Accordingly, both compounds, and ibuprofen, act as strong partial agonists. Assessment of NSAID activities in PPARγ-dependent 3T3-L1 cells reveals that NSAIDs display adipogenic activities and exclusively regulate PPARγ-dependent target genes in a manner that is consistent with their observed binding modes. Further, PPARγ knockdown eliminates indomethacin activities at selected endogenous genes, confirming receptor-dependence of observed effects. We propose that it is important to consider how individual NSAIDs interact with PPARγ to understand their activities, and that it will be interesting to determine whether high dose NSAID therapies result in PPAR activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.