Affinage

PPARG

Peroxisome proliferator-activated receptor gamma · UniProt P37231

Length
505 aa
Mass
57.6 kDa
Annotated
2026-06-10
100 papers in source corpus 29 papers cited in narrative 29 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPARγ is a ligand-activated nuclear receptor that, upon binding thiazolidinedione drugs and other ligands, drives cofactor docking and transcriptional programs governing adipogenesis, lipid and glucose metabolism, and inflammation (PMID:9568680). Activated PPARγ heterodimerizes with RXR, recruits cofactors, and binds PPAR-responsive elements (PPREs) to stimulate metabolic target genes (PMID:12055342); direct, ChIP-validated targets include klotho (PMID:18547997), the glycolytic enzymes HK2 and PKM2 in fatty liver (PMID:22334075), FXR in adipocytes (PMID:32446390), LPIN1 in mammary epithelium (PMID:35149744), and the osteocyte gene Sost/sclerostin (PMID:33722775). Its output is tuned by post-translational modification and cofactor exchange: ERK1/2 phosphorylates a serine that attenuates transactivation while MEK1/2 binds nuclear PPARγ and exports it to the cytoplasm (PMID:17611413), and CDK5 phosphorylates S273/S245, a modification that recruits Thrap3 to reprogram diabetic gene expression and that ligand binding can allosterically block from a distal site (PMID:25316675, PMID:32239932). PPARγ stability is controlled by ubiquitin-proteasome turnover triggered by FABP4 (PMID:24319114) and by direct binding of MAGED1, which suppresses receptor stability and activity (PMID:30121577). Cofactor balance determines activation versus repression: lipin1 displaces the NCoR1/SMRT co-repressors to activate the receptor (PMID:23627357), whereas CACUL1 binds a CoRNR-box motif and represses PPARγ by reciprocally tuning SIRT1/LSD1 recruitment and histone H3K9 modifications (PMID:29233982); PPARG2 expression itself is gated by an HDAC1/HDAC3 co-repressor complex tethered via sumoylated CEBPD (PMID:18619497). Beyond adipocytes, PPARγ exerts cell-type-specific roles in bone, where pS112 and pS273 differentially control osteoblastic and osteoclastic activity (PMID:27422345, PMID:33722775), in macrophages and inflammation (PMID:19850645, PMID:38648706), and in sensory neurons, where it undergoes dynein-dependent retrograde axonal transport supporting regeneration (PMID:26446277). Structural studies of inverse agonists (SR2595, SR10171) demonstrate that pharmacological repression of PPARγ promotes osteogenic differentiation and increases bone mass (PMID:26068133, PMID:27422345).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Established PPARγ as the molecular target of insulin-sensitizing thiazolidinediones, linking a nuclear receptor to systemic glucose control via ligand-dependent transcription.

    Evidence nuclear receptor ligand-binding and transcriptional reporter assays

    PMID:9568680

    Open questions at the time
    • Endogenous physiological ligands not defined
    • Tissue-specific target gene sets not yet mapped
  2. 2002 High

    Defined the core transcriptional mechanism: ligand-activated PPARγ heterodimerizes with RXR and binds PPREs to activate metabolic genes.

    Evidence Co-IP, reporter assays, and ChIP

    PMID:12055342

    Open questions at the time
    • Genome-wide target catalog incomplete
    • Cofactor specificity by cell type unresolved
  3. 2005 Medium

    Showed that PPARγ activity is dynamically restrained by MAPK signaling through ERK-mediated serine phosphorylation and MEK1/2-driven nuclear export, a non-genomic spatial control mechanism.

    Evidence Co-IP, subcellular fractionation, phosphorylation assays, and NES mutagenesis

    PMID:17611413

    Open questions at the time
    • Single-lab findings
    • Quantitative contribution of export to physiological output unknown
  4. 2008 High

    Identified multiple layers of negative regulation — FABP4-driven ubiquitination/degradation, TNF-α/IKK-mediated suppression, and sumoylated-CEBPD-tethered HDAC repressor complexes at the PPARG2 promoter — clarifying how receptor abundance and PPARG2 transcription are dampened.

    Evidence ubiquitination/proteasome assays, FABP4 knockout/complementation, kinase inhibition, promoter mapping, ChIP, and sumoylation-mutant analysis

    PMID:18619497 PMID:18655773 PMID:24319114

    Open questions at the time
    • E3 ligase mediating FABP4-triggered ubiquitination not identified
    • Interplay among these repressive inputs not integrated
  5. 2008 High

    Extended the direct target repertoire by demonstrating PPARγ binds a noncanonical PPRE in the klotho promoter, connecting the receptor to renal klotho expression in vivo.

    Evidence ChIP, EMSA, reporter assays, and in vivo agonist treatment

    PMID:18547997

    Open questions at the time
    • Physiological consequence of klotho induction not fully defined
  6. 2012 High

    Placed PPARγ within an Akt2-controlled circuit driving glycolytic gene expression (HK2, PKM2) in PTEN-null fatty liver, linking the receptor to steatosis and tumorigenesis.

    Evidence ChIP and genetic mouse epistasis (PTEN-null, Akt2 knockout)

    PMID:22334075

    Open questions at the time
    • Generality beyond PTEN-null context unknown
  7. 2013 High

    Resolved a ligand-independent activation route: lipin1 binds via a VXXLL motif and a unique TAD to displace NCoR1/SMRT co-repressors, activating PPARγ and adipogenesis.

    Evidence reciprocal Co-IP, pulldown, domain mutagenesis, reporter assays, and ChIP

    PMID:23627357

    Open questions at the time
    • In vivo relevance of lipin1-driven activation not quantified
  8. 2014 High

    Defined how the diabetes-associated CDK5-S273 phosphorylation is decoded — Thrap3 binds the phosphorylated receptor to reprogram adipocyte gene expression — and showed Gcn5/PCAF acetyltransferases act upstream by enabling Pol II elongation of Pparg transcripts.

    Evidence Co-IP/MS, knockdown, in vivo antisense rescue, double-knockout with ectopic-PPARγ rescue, and Pol II ChIP

    PMID:25071153 PMID:25316675

    Open questions at the time
    • Full Thrap3-dependent gene program not delineated
    • Acetyltransferase mechanism on other loci unclear
  9. 2015 High

    Used structure-guided design to develop SR1664-derived inverse agonists (SR2595) that repress PPARγ and redirect bone-marrow MSCs toward osteogenesis, establishing antagonism as a route to alter cell fate.

    Evidence X-ray crystallography and MSC differentiation assays

    PMID:26068133

    Open questions at the time
    • Long-term in vivo efficacy and selectivity not established
  10. 2016 Medium

    Demonstrated that distinct phosphosites partition PPARγ's skeletal effects (pS112 → osteoblastic, pS273 → osteoclastic), with SR10171 selectively blocking pS273 to increase bone and normalize metabolism, and described isoform-specific sumoylation/cytoplasmic localization in lipid-synthesizing meibocytes.

    Evidence in vivo mouse models with phospho-specific antibodies, bone histomorphometry, and subcellular fractionation with anti-SUMO1 immunoblotting

    PMID:27422345 PMID:27531629

    Open questions at the time
    • Single-lab phenotypes
    • Mechanistic link between sumoylation and cytoplasmic retention not fully resolved
  11. 2017 High

    Identified CACUL1 as a CoRNR-box co-repressor that represses PPARγ by reciprocally tuning SIRT1/LSD1 recruitment and H3K9 acetylation/methylation, refining the epigenetic logic of receptor output.

    Evidence Co-IP with domain mapping, histone-mark ChIP, RNA-seq, and knockdown

    PMID:29233982

    Open questions at the time
    • Physiological adipose role of CACUL1 not tested in vivo
  12. 2018 Medium

    Showed MAGED1 directly binds and destabilizes PPARγ, with MAGED1 loss increasing receptor levels, adipocyte precursors, and insulin sensitivity, adding a stability-control input to the network.

    Evidence Co-IP, protein stability assays, and MAGED1 knockout mice

    PMID:30121577

    Open questions at the time
    • Single-lab study
    • Degradation machinery engaged by MAGED1 unspecified
  13. 2020 High

    Provided high-resolution mechanism for ligand-mediated suppression of pathogenic phosphorylation: CDK5 modifies S245/S273, and ligand binding allosterically blocks CDK5 docking from a distal site, and identified TMEM18 as an upstream activator of the PPARG1 promoter required for adipogenesis.

    Evidence X-ray/NMR/HDX/MD with mutagenesis; promoter reporter assays with zebrafish and human preadipocyte loss-of-function

    PMID:32239932 PMID:33086065

    Open questions at the time
    • How TMEM18 reaches the promoter mechanistically unknown
    • Structural model of full-length receptor-CDK5 complex incomplete
  14. 2021 High

    Established cell-type-specific in vivo functions: osteocyte PPARγ directly drives Sost/sclerostin via promoter PPREs, and bladder urothelial PPARγ governs differentiation versus immune-deserted tumor formation depending on progenitor state.

    Evidence conditional/transgenic mouse models, ChIP with PPRE mutagenesis, and histology/expression analysis

    PMID:33722775 PMID:34697317

    Open questions at the time
    • Context-dependence of tumor-promoting versus protective output not mechanistically reconciled
  15. 2024 Medium

    Linked PPARγ activation to anti-inflammatory autophagy: agonism accelerates ROS clearance to limit macrophage polarization and NLRP3 inflammasome activation in arthritis models.

    Evidence RAW264.7 assays, CIA rat model, autophagy flux, ROS and NLRP3 readouts

    PMID:38648706

    Open questions at the time
    • Direct transcriptional targets mediating autophagy not identified
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the competing stability inputs (FABP4, MAGED1), cofactor exchanges (lipin1, CACUL1, Thrap3), and phosphorylation states are integrated to specify distinct tissue programs — and which endogenous ligands drive each — remains unresolved.
  • No unified model linking PTM state to cofactor selection per cell type
  • Endogenous ligand identity per context undefined
  • E3 ligases controlling degradation not fully identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0008289 lipid binding 1
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-168256 Immune System 3
Partners
CACUL1CDK5FABP4LIPIN1MAGED1MEK1/2RXRTHRAP3
Complex memberships
PPARγ-RXR heterodimer

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 PPARγ was identified as the major functional receptor for the thiazolidinedione class of insulin-sensitizing drugs; ligand binding by PPARγ leads to cofactor docking in a ligand-dependent fashion, regulating transcriptional activity in adipogenesis and systemic insulin action. Nuclear receptor biochemistry, ligand binding assays, transcriptional reporter assays Diabetes High 9568680
2002 Upon activation, PPARγ heterodimerizes with retinoid X receptor (RXR), recruits specific cofactors, and binds to PPAR-responsive DNA elements to stimulate transcription of target genes involved in glucose and lipid metabolism. Co-immunoprecipitation, reporter assays, chromatin immunoprecipitation Annual review of nutrition High 12055342
2005 PPARγ activity is regulated by ERK1/2-mediated phosphorylation of a serine residue, which attenuates its transactivation function; additionally, mitogen-activated MEK1/2 interacts directly with nuclear PPARγ and exports it from the nucleus via MEK's N-terminal nuclear export signal, providing a nucleo-cytoplasmic shuttling mechanism. Co-immunoprecipitation, subcellular fractionation, phosphorylation assays, nuclear export signal mutagenesis Cell cycle (Georgetown, Tex.) Medium 17611413
2008 FABP4 triggers the ubiquitination and subsequent proteasomal degradation of PPARγ, thereby downregulating PPARγ protein levels; FABP4-null preadipocytes show increased PPARγ expression and enhanced adipogenesis, and complementation of FABP4 reverses this. Ubiquitination assays, proteasome inhibitor experiments, FABP4 knockout and complementation in preadipocytes and macrophages, Western blotting Diabetes High 24319114
2008 Klotho is a direct transcriptional target of PPARγ; a noncanonical PPAR-responsive element in the 5'-flanking region of the human klotho gene was identified by ChIP and gel shift assays, and PPARγ agonists increased klotho expression in vivo in mouse kidneys. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), promoter-reporter assays, siRNA knockdown, in vivo adenovirus overexpression Kidney international High 18547997
2008 TNF-α inhibits PPARγ activity via activation of serine kinases including IKK, ERK, JNK, and p38; IKK acts as a dominant regulator by both inhibiting PPARγ expression and activating PPARγ corepressors. Kinase activity assays, gene expression analysis, pharmacological kinase inhibition Biochemical and biophysical research communications Medium 18655773
2008 HDAC1 and HDAC3 are recruited to the PPARG2 promoter via sumoylated CEBPD (sumoylation at lysine 120 by SUMO1), forming a repressor complex that inactivates PPARG2 transcription; non-sumoylated CEBPD reverses this repression to activate PPARG2 during hepatic lipogenesis. 5'-serial deletion reporter assays, ChIP, co-immunoprecipitation of CEBPD-HDAC1/HDAC3, sumoylation mutant analysis Biochimica et biophysica acta High 18619497
2012 PPARγ directly binds to the promoters of hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2) to activate their transcription in PTEN-null fatty liver; this activity and liver steatosis/tumorigenesis are under control of Akt2 kinase upstream. Chromatin immunoprecipitation, promoter binding assays, genetic mouse models (PTEN-null, Akt2 knockout) Nature communications High 22334075
2013 Lipin1 directly interacts with PPARγ through a VXXLL motif (residue 885) and a C-terminal region (residues 825–926), releasing co-repressors NCoR1 and SMRT from PPARγ in the absence of ligand, thereby activating PPARγ transcriptional activity and enhancing adipocyte differentiation; a novel transcriptional activation domain (TAD, residues 217–399) unique to lipin1 mediates PPARγ activation but not PPARα. Co-immunoprecipitation, pulldown, reporter assays, domain mutagenesis (VXXLL mutant), chromatin immunoprecipitation The Biochemical journal High 23627357
2014 Thrap3 (thyroid hormone receptor-associated protein 3) directly interacts with PPARγ when it is phosphorylated at Ser273 by CDK5; this interaction controls CDK5-mediated diabetic gene programming in adipocytes, including dysregulation of adiponectin and adipsin. Co-immunoprecipitation, mass spectrometry, siRNA knockdown, antisense oligonucleotide treatment in vivo, gene expression profiling Genes & development High 25316675
2014 Gcn5 and PCAF acetyltransferases act upstream of PPARγ to facilitate adipogenesis by regulating RNA polymerase II elongation of PPARγ transcripts; double knockout of Gcn5/PCAF inhibits PPARγ expression and prevents adipocyte differentiation, which is rescued by ectopic PPARγ expression. Genetic knockout (double KO), ectopic PPARγ expression rescue, RNA pol II ChIP, quantitative gene expression Molecular and cellular biology High 25071153
2015 Structural analysis of PPARγ revealed the mechanism by which the antagonist SR1664 actively antagonizes PPARγ; this enabled development of SR2595 as an inverse agonist that represses PPARγ and promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells. X-ray crystallography, structural biology, cell differentiation assays with bone marrow-derived MSCs Nature communications High 26068133
2015 PPARγ protein and mRNA are present within sensory axons; after sciatic nerve injury, PPARγ protein levels increase in axons with increased retrograde transport via association with dynein, and PPARγ accumulates in the nucleus of sensory neuron cell bodies; PPARγ antagonists attenuate axonal regeneration. Immunofluorescence localization, subcellular fractionation, retrograde transport assays, co-immunoprecipitation with dynein, loss-of-function with PPARγ antagonists Developmental neurobiology Medium 26446277
2016 Post-translational modifications of PPARγ at S112 and S273 differentially regulate bone biology: pS112 controls osteoblastic activity and pS273 controls osteoclastic activity; the inverse agonist SR10171 blocks pS273 but not pS112, increasing trabecular/cortical bone and normalizing metabolic parameters in vivo. In vivo mouse models (normoglycemic and hyperglycemic), phospho-specific antibodies, bone histomorphometry, pharmacological intervention EBioMedicine Medium 27422345
2016 PPARγ directly binds to PPAR-responsive elements (PPRE) in the FXR gene promoter in adipocytes (demonstrated by ChIP), activating FXR expression in a PPARγ agonist-dependent manner; FXR in turn binds FXRE in the SCD gene promoter to promote lipogenesis. Chromatin immunoprecipitation (ChIP), promoter reporter assays, site mutagenesis Biochemical and biophysical research communications Medium 32446390
2017 CACUL1 directly binds to PPARγ through a CoRNR box 2 motif and represses PPARγ transcriptional activity and adipogenesis; CACUL1 depletion results in increased histone H3K9 acetylation and decreased H3K9 methylation at PPARγ-responsive gene promoters, through reciprocal regulation of SIRT1 and LSD1 recruitment. Co-immunoprecipitation, ChIP for histone marks, RNA-seq, siRNA knockdown, domain mutagenesis Cell death & disease High 29233982
2018 MAGED1 directly binds to PPARγ and suppresses its stability and transcriptional activity; MAGED1-deficient mice show increased PPARγ protein levels, more adipocyte precursors, and hyperplasia of white adipose tissue, along with improved insulin sensitivity. Co-immunoprecipitation, protein stability assays, MAGED1 knockout mice, gene expression analysis The Journal of endocrinology Medium 30121577
2020 Structural and conformational analysis (X-ray crystallography, NMR, HDX, MD simulations, site-directed mutagenesis) revealed that CDK5 phosphorylates PPARγ at S245 (equivalent to S273 in full-length); ligand binding can allosterically block CDK5 interaction with PPARγ from a distal site, inhibiting phosphorylation via conformational change. X-ray crystallography, NMR, HDX, protein-protein docking, MD simulations, site-directed mutagenesis Journal of medicinal chemistry High 32239932
2020 TMEM18 activates PPARG, particularly upregulating PPARG1 promoter activity; TMEM18 knockdown impairs adipocyte formation in zebrafish and human preadipocytes, placing TMEM18 upstream of PPARγ as a regulator of adipogenesis. Promoter reporter assays, siRNA knockdown, zebrafish loss-of-function, human preadipocyte differentiation assays Cell reports Medium 33086065
2021 PPARγ in osteocytes is essential for sclerostin (SOST) production; PPARγ directly binds to PPREs in the 8 kb upstream region of the Sost gene promoter, as shown by ChIP; osteocyte-specific PPARγ deletion (γOTKO) results in increased bone mass, reduced bone marrow adiposity, and protection from TZD-induced bone loss. Osteocyte-specific conditional knockout mice (Dmp1Cre), ChIP for PPARG binding at Sost promoter PPREs, site mutagenesis, gene expression correlation analysis Bone High 33722775
2009 PPARγ activation by rosiglitazone in macrophages represses fractalkine receptor (FR) gene transcription and prevents FR plasma membrane translocation; in endothelial cells, rosiglitazone impedes nuclear export of fractalkine (FKN), revealing a novel anti-inflammatory mechanism of PPARγ. Gene expression analysis, subcellular fractionation/immunofluorescence for receptor localization, nuclear export assays Journal of molecular endocrinology Medium 19850645
2009 PPARγ modulates hypothalamic TRH regulation in vivo; PPARγ agonist injection modified TRH-luc transcription in newborn mouse hypothalamus; PPARγ overexpression abrogated T3-dependent Trh repression, while RXRα overexpression rescued this effect, indicating competition for RXR as a mechanism of crosstalk between PPARγ and TRβ. In vivo intracerebral injection, reporter gene (TRH-luc) assay, shRNA knockdown, adenoviral overexpression, qPCR Molecular and cellular endocrinology Medium 19900503
2022 C/EBPβ (LAP* and LAP isoforms) together with CSF2 signaling selectively induces expression of Pparg isoform 2 but not isoform 1 in alveolar macrophages; C/EBPβ-deficient AMs show severe defects in proliferation, phagocytosis, and lipid metabolism causing a PAP-like syndrome. Transcriptome analysis, chromatin accessibility (ATAC-seq), conditional knockout mice, functional assays (proliferation, phagocytosis, lipid metabolism) Science immunology Medium 36112694
2016 PPARγ activation with rosiglitazone stimulates lipid synthesis in mouse meibocytes, associated with SUMO1 sumoylation of the 72 kDa PPARγ isoform and its cytoplasmic accumulation; loss of cytoplasmic PPARγ was observed in aged atrophic meibomian glands. Subcellular fractionation, immunoblotting (anti-SUMO1), CARS/Raman microspectroscopy, LipidTox staining, mRNA quantification The ocular surface Medium 27531629
2021 Pparg activation in basal bladder urothelial progenitors induces superficial cell formation and cell cycle exit, preventing tumor formation; however, in injury-activated progenitors, Pparg activation results in luminal tumor formation that is immune-deserted, linked to downregulation of NF-κB as a Pparg target. Transgenic mouse model (VP16;Pparg activated form), in situ histology, immunofluorescence, gene expression analysis Nature communications Medium 34697317
2010 PPARγ activation promotes osteoclastogenesis through a transcriptional network comprising PPARγ, PGC-1β, and ERRα, which promotes both osteoclast differentiation and mitochondrial activation; PPARγ also suppresses osteoblastogenesis, creating dual opposing effects on bone homeostasis. Genetic mouse models, cell differentiation assays, gene expression analysis, reporter assays Trends in endocrinology and metabolism: TEM Medium 20863714
2009 PPARγ plays a pivotal role in controlling placental vascular proliferation; PPARγ-null embryos show unsettled balance of pro- (proliferin/PLF) and anti-angiogenic factors (proliferin-related protein/PRP), and PPARγ agonist rosiglitazone treatment disrupts placental vasculature and decreases proangiogenic gene expression. Conditional knockout mice (Sox2Cre/PPARγL2/L2), in vivo rosiglitazone treatment, gene expression analysis Endocrinology Medium 20810566
2022 PPARγ directly regulates buffalo LPIN1 transcription by binding to two PPAR response elements (PPRE1 and PPRE2) identified in the core LPIN1 promoter region (−666 to +42 bp); site mutagenesis confirmed both PPREs are required for PPARγ-dependent LPIN1 activation and triglyceride synthesis in mammary epithelial cells. Chromatin immunoprecipitation, promoter reporter assays, site-directed mutagenesis of PPREs, overexpression/knockdown Scientific reports Medium 35149744
2024 PPARG activation promotes autophagy to accelerate ROS clearance, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation in rheumatoid arthritis; CBD acts as a PPARγ agonist mediating this pathway. In vitro RAW264.7 cell assays, CIA rat model, autophagy flux assays, ROS measurement, NLRP3 inflammasome assays Journal of autoimmunity Medium 38648706

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Fat and beyond: the diverse biology of PPARgamma. Annual review of biochemistry 1710 18518822
1998 PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes 1484 9568680
2005 The many faces of PPARgamma. Cell 1215 16360030
1999 PPARgamma, the ultimate thrifty gene. Diabetologia 513 10447513
2014 Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochemical pharmacology 444 25083916
2009 Wnt and PPARgamma signaling in osteoblastogenesis and adipogenesis. Nature reviews. Rheumatology 423 19581903
2002 PPAR(gamma) and glucose homeostasis. Annual review of nutrition 361 12055342
2005 Regulation of PPARgamma activity during adipogenesis. International journal of obesity (2005) 347 15711576
2013 FABP4 attenuates PPARγ and adipogenesis and is inversely correlated with PPARγ in adipose tissues. Diabetes 272 24319114
2002 Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands: a review. Domestic animal endocrinology 193 11900961
2016 PPARγ signaling and emerging opportunities for improved therapeutics. Pharmacological research 186 27268145
2014 Transcriptional and epigenetic regulation of PPARγ expression during adipogenesis. Cell & bioscience 184 24904744
2017 Peroxisome proliferator-activated receptor γ (PPARγ): A master gatekeeper in CNS injury and repair. Progress in neurobiology 182 29032144
2007 PPARgamma in human and mouse physiology. Biochimica et biophysica acta 175 17475546
2010 The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. American journal of epidemiology 158 20179158
2008 Regulation of PPARgamma function by TNF-alpha. Biochemical and biophysical research communications 149 18655773
2008 Klotho is a target gene of PPAR-gamma. Kidney international 147 18547997
2018 The CD36-PPARγ Pathway in Metabolic Disorders. International journal of molecular sciences 142 29883404
2011 Minireview: PPARγ as the target of obesogens. The Journal of steroid biochemistry and molecular biology 141 21251979
2012 PPARγ contributes to PKM2 and HK2 expression in fatty liver. Nature communications 132 22334075
2009 Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation. The American journal of clinical nutrition 130 19906796
2008 The many faces of PPARgamma: anti-inflammatory by any means? Immunobiology 125 18926294
2010 PPARγ in bone homeostasis. Trends in endocrinology and metabolism: TEM 121 20863714
2007 MAPK kinases as nucleo-cytoplasmic shuttles for PPARgamma. Cell cycle (Georgetown, Tex.) 120 17611413
2015 Pharmacological repression of PPARγ promotes osteogenesis. Nature communications 108 26068133
2003 Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands as bifunctional regulators of cell proliferation. Biochemical pharmacology 107 14555212
2010 PPARgamma in placental angiogenesis. Endocrinology 94 20810566
2010 Brown vs white adipocytes: the PPARgamma coregulator story. FEBS letters 90 20600006
2003 Alanine for proline substitution in the peroxisome proliferator-activated receptor gamma-2 (PPARG2) gene and the risk of incident myocardial infarction. Arteriosclerosis, thrombosis, and vascular biology 88 12663371
2011 Epigenetic codes of PPARγ in metabolic disease. FEBS letters 85 21605560
2016 The role of PPARgamma in cardiovascular diseases. Physiological research 82 27775420
2021 Pparg signaling controls bladder cancer subtype and immune exclusion. Nature communications 79 34697317
2017 PPARγ and Its Role in Cardiovascular Diseases. PPAR research 77 28243251
2016 PPARγ Regulates Mouse Meibocyte Differentiation and Lipid Synthesis. The ocular surface 77 27531629
2021 The Role of PPAR-γ in Allergic Disease. Current allergy and asthma reports 75 34697644
2016 PPARG Post-translational Modifications Regulate Bone Formation and Bone Resorption. EBioMedicine 71 27422345
2009 Peroxisome proliferator-activated receptor gamma (PPARgamma): Is the genomic activity the only answer? Steroids 71 19900469
2015 Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Ligand Choreography: Newcomers Take the Stage. Journal of medicinal chemistry 69 25734377
2004 Role of PPARgamma in macrophage biology and atherosclerosis. Trends in endocrinology and metabolism: TEM 69 15541649
2020 ACSL1 affects Triglyceride Levels through the PPARγ Pathway. International journal of medical sciences 65 32218693
2005 PPARgamma and atherosclerosis. Current medical research and opinion 63 15811195
2014 Gcn5 and PCAF regulate PPARγ and Prdm16 expression to facilitate brown adipogenesis. Molecular and cellular biology 57 25071153
2010 PPARgamma and the pathobiology of pulmonary arterial hypertension. Advances in experimental medicine and biology 55 20204748
2011 PPARγ and human trophoblast differentiation. Journal of reproductive immunology 53 21704384
2008 The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 53 18317437
2020 Minutes of PPAR-γ agonism and neuroprotection. Neurochemistry international 52 32758586
2014 Thrap3 docks on phosphoserine 273 of PPARγ and controls diabetic gene programming. Genes & development 51 25316675
2024 PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis. Journal of autoimmunity 50 38648706
2008 PPARgamma and MEK Interactions in Cancer. PPAR research 50 18596912
2013 Pro12Ala variant of the PPARG2 gene increases body mass index: An updated meta-analysis encompassing 49,092 subjects. Obesity (Silver Spring, Md.) 49 23666678
2000 PPARgamma: observations in the hematopoietic system. Prostaglandins & other lipid mediators 49 10936415
2021 The PPARg System in Major Depression: Pathophysiologic and Therapeutic Implications. International journal of molecular sciences 47 34502154
2023 Cannabidiol goes nuclear: The role of PPARγ. Phytomedicine : international journal of phytotherapy and phytopharmacology 46 36965374
2017 Lysophospholipid-Related Diseases and PPARγ Signaling Pathway. International journal of molecular sciences 46 29258184
2013 Lipin1 regulates PPARγ transcriptional activity. The Biochemical journal 46 23627357
2008 HDAC1/HDAC3 modulates PPARG2 transcription through the sumoylated CEBPD in hepatic lipogenesis. Biochimica et biophysica acta 46 18619497
2020 The Obesity-Susceptibility Gene TMEM18 Promotes Adipogenesis through Activation of PPARG. Cell reports 44 33086065
2005 Atypical transcriptional regulators and cofactors of PPARgamma. International journal of obesity (2005) 44 15711575
2021 PPARG in osteocytes controls sclerostin expression, bone mass, marrow adiposity and mediates TZD-induced bone loss. Bone 43 33722775
2011 Role of PPARg2 transcription factor in thiazolidinedione-induced insulin sensitization. The Journal of pharmacy and pharmacology 43 22221092
2023 A glimpse of the connection between PPARγ and macrophage. Frontiers in pharmacology 42 37701041
2013 PPARγ against tumors by different signaling pathways. Onkologie 41 24107916
2022 C/EBPβ regulates lipid metabolism and Pparg isoform 2 expression in alveolar macrophages. Science immunology 38 36112694
2009 PPARgamma in Kidney Physiology and Pathophysiology. PPAR research 38 19283081
2016 Commonalities in the Association between PPARG and Vitamin D Related with Obesity and Carcinogenesis. PPAR research 37 27579030
2018 miR-128-3p regulates 3T3-L1 adipogenesis and lipolysis by targeting Pparg and Sertad2. Journal of physiology and biochemistry 36 29654510
2017 Micro-RNA-130a-3p Regulates Gemcitabine Resistance via PPARG in Cholangiocarcinoma. Annals of surgical oncology 36 28560603
2010 The role of PPARγ for the osteoblastic differentiation. Journal of endocrinological investigation 36 20938219
2023 PPARγ activation suppresses chondrocyte ferroptosis through mitophagy in osteoarthritis. Journal of orthopaedic surgery and research 33 37620972
2006 Nuclear receptor corepressors and PPARgamma. Nuclear receptor signaling 33 16604166
2023 Bavachinin Ameliorates Rheumatoid Arthritis Inflammation via PPARG/PI3K/AKT Signaling Pathway. Inflammation 31 37358659
2015 Axonal PPARγ promotes neuronal regeneration after injury. Developmental neurobiology 31 26446277
2012 PPARγ and stress: implications for aging. Experimental gerontology 31 22960592
2007 Peroxisome proliferator-activated receptor gamma (PPARgamma) and colorectal carcinogenesis. Journal of cancer research and clinical oncology 31 17659359
2020 Assessing the receptor-mediated activity of PAHs using AhR-, ERα- and PPARγ- CALUX bioassays. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 30 32738369
2021 PPARγ Regulates Triclosan Induced Placental Dysfunction. Cells 29 35011648
2020 Photohormones Enable Optical Control of the Peroxisome Proliferator-Activated Receptor γ (PPARγ). Journal of medicinal chemistry 29 32886507
2017 CACUL1 reciprocally regulates SIRT1 and LSD1 to repress PPARγ and inhibit adipogenesis. Cell death & disease 29 29233982
2023 PPARG: A Promising Therapeutic Target in Breast Cancer and Regulation by Natural Drugs. PPAR research 28 37334066
2020 Insights into PPARγ Phosphorylation and Its Inhibition Mechanism. Journal of medicinal chemistry 27 32239932
2020 Promotion of lipogenesis by PPARγ-activated FXR expression in adipocytes. Biochemical and biophysical research communications 27 32446390
2021 Analysis of PPARγ Signaling Activity in Psoriasis. International journal of molecular sciences 26 34445309
2019 YAP1 regulates PPARG and RXR alpha expression to affect the proliferation and differentiation of ovine preadipocyte. Journal of cellular biochemistry 25 31297878
2019 Sirt1 inhibits gouty arthritis via activating PPARγ. Clinical rheumatology 25 31367941
2016 PPARγ in Bacterial Infections: A Friend or Foe? PPAR research 25 27774097
2015 PPARγ Maintains Homeostasis through Autophagy Regulation in Dental Pulp. Journal of dental research 24 25744070
2010 PPARγ and chronic kidney disease. Pediatric nephrology (Berlin, Germany) 24 20676693
2009 Rosiglitazone activation of PPARgamma suppresses fractalkine signaling. Journal of molecular endocrinology 24 19850645
2022 LPIN1 promotes triglycerides synthesis and is transcriptionally regulated by PPARG in buffalo mammary epithelial cells. Scientific reports 23 35149744
2021 Glitazones, PPAR-γ and Neuroprotection. Mini reviews in medicinal chemistry 23 33663364
2002 Biology and toxicology of PPARgamma ligands. Human & experimental toxicology 22 12412636
2020 PPARγ Agonists in Combination Cancer Therapies. Current cancer drug targets 21 31814555
2018 Inhibition of PPARγ, adipogenesis and insulin sensitivity by MAGED1. The Journal of endocrinology 20 30121577
2009 Peroxisome proliferator-activated receptor-gamma (PPARgamma) modulates hypothalamic Trh regulation in vivo. Molecular and cellular endocrinology 20 19900503
2008 CXCR4 in Cancer and Its Regulation by PPARgamma. PPAR research 20 18779872
2020 PPARγ and RhoBTB1 in hypertension. Current opinion in nephrology and hypertension 19 31789920
2020 In-Vitro-Generated Hypertrophic-Like Adipocytes Displaying PPARG Isoforms Unbalance Recapitulate Adipocyte Dysfunctions In Vivo. Cells 18 32455814
2021 Ups and downs: The PPARγ/p-PPARγ seesaw of follistatin-like 1 and integrin receptor signaling in adipogenesis. Molecular metabolism 17 34813964
2024 Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway. Lipids in health and disease 16 38468335
2018 Reversing the curse on PPARγ. The Journal of clinical investigation 16 29757190

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