ArticleThe Journal of clinical investigation2018
PPARγ deacetylation dissociates thiazolidinedione's metabolic benefits from its adverse effects.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
The trial behind it
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
42 citing papers in PubMed, 55 citations in OpenAlex.
- Interplay of Ser273 Phosphorylation and K268 and K293 Acetylation in PPARγ: Implications for PPARγ Activation.Proteins · 2026Article
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- Caspase-6 Controls Lipid and Energy Metabolism in Diet-Induced Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial retrograde signal through GCN5L1 transition-mediated PPARγ stabilization promotes MASLD development.JCI insight · 2026Article
- Visceral and Subcutaneous Fat Deposits Exhibit Distinct Roles in the Initiation and Progression of Breast Cancer.Breast cancer (Dove Medical Press) · 2026Article
- Small molecule inhibitor of PPARγ acetylation promotes insulin sensitization and browning of white adipose tissue with improved safety.bioRxiv : the preprint server for biology · 2025Article
- Article
- Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.International journal of molecular sciences · 2025Review
- Review
- Screening Based on Structural and Biological Verification of Stachyose as a PPARγ-Modulating Ligand for the Treatment of Non-Alcoholic Fatty Liver Disease.Food science & nutrition · 2025Article
- PPARγ acetylation governs mammary adenocarcinoma tumor growth via acetylated residues that determine DNA sequence-specific binding.Oncogene · 2025Article
- The Many Facets of PPAR-γ Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions.Current obesity reports · 2025Review
- Bone marrow adipocytes: key players in vascular niches, aging, and disease.Frontiers in cell and developmental biology · 2025Review
- Progress in understanding how clock genes regulate aging and associated metabolic processes.Frontiers in physiology · 2025Review
- The Effect of an Innovative Combination of Bergamot Polyphenolic Fraction andInternational journal of molecular sciences · 2023Article
- PPARγ Acetylation in Adipocytes Exacerbates BAT Whitening and Worsens Age-Associated Metabolic Dysfunction.Cells · 2023Article
- Review
- Role of hepatic peroxisome proliferator-activated receptor γ in non-alcoholic fatty liver disease.The Journal of endocrinology · 2023Review
- PPARγ Acetylation Orchestrates Adipose Plasticity and Metabolic Rhythms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Reflections on the state of diabetes research and prospects for treatment.Diabetology international · 2023Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Thiazolidinediones (TZDs) are PPARγ agonists with potent insulin-sensitizing effects. However, their use has been curtailed by substantial adverse effects on weight, bone, heart, and hemodynamic balance. TZDs induce the deacetylation of PPARγ on K268 and K293 to cause the browning of white adipocytes. Here, we show that targeted PPARγ mutations resulting in constitutive deacetylation (K268R/K293R, 2KR) increased energy expenditure and protected from visceral adiposity and diet-induced obesity by augmenting brown remodeling of white adipose tissues. Strikingly, when 2KR mice were treated with rosiglitazone, they maintained the insulin-sensitizing, glucose-lowering response to TZDs, while displaying little, if any, adverse effects on fat deposition, bone density, fluid retention, and cardiac hypertrophy. Thus, deacetylation appears to fulfill the goal of dissociating the metabolic benefits of PPARγ activation from its adverse effects. Strategies to leverage PPARγ deacetylation may lead to the design of safer, more effective agonists of this nuclear receptor in the treatment of metabolic diseases.
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What OpenQuestion holds
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.