ArticleThe Journal of clinical investigation2010
Proteasomal degradation of retinoid X receptor alpha reprograms transcriptional activity of PPARgamma in obese mice and humans.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- The RBM14/CoAA-interacting, long intergenic non-coding RNA Paral1 regulates adipogenesis and coactivates the nuclear receptor PPARγ.Scientific reports · 2017Trial
- Effects of resveratrol on growth performance, meat quality, and intramuscular fat deposition in finishing steers.Journal of animal science · 2025Article
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- The DuckAnimals : an open access journal from MDPI · 2023Article
- A Novel in Duck Myoblasts: The Transcription Factor Retinoid X Receptor Alpha (RXRA) Inhibits Lipid Accumulation by Promoting CD36 Expression.International journal of molecular sciences · 2023Article
- Obesity and pregnancy, the perfect metabolic storm.European journal of clinical nutrition · 2021Review
- Comparative Proteomic Analysis of Visceral Adipose Tissue in Morbidly Obese and Normal Weight Chinese Women.International journal of endocrinology · 2019Article
- Targeting Peroxisome Proliferator-Activated Receptor γ to Increase Estrogen-Induced Apoptosis in Estrogen-Deprived Breast Cancer Cells.Molecular cancer therapeutics · 2018Article
- PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity.International journal of molecular sciences · 2018Review
- Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer.World journal of gastroenterology · 2016Review
- Metformin interferes with bile acid homeostasis through AMPK-FXR crosstalk.The Journal of clinical investigation · 2014Article
- Peroxisome proliferator-activated receptor γ regulates genes involved in insulin/insulin-like growth factor signaling and lipid metabolism during adipogenesis through functionally distinct enhancer classes.The Journal of biological chemistry · 2014Article
- A dynamic CTCF chromatin binding landscape promotes DNA hydroxymethylation and transcriptional induction of adipocyte differentiation.Nucleic acids research · 2014Article
- Differential proinflammatory and oxidative stress response and vulnerability to metabolic syndrome in habitual high-fat young male consumers putatively predisposed by their genetic background.International journal of molecular sciences · 2013Article
- PPARγ signaling and metabolism: the good, the bad and the future.Nature medicine · 2013Review
- THRAP3 interacts with HELZ2 and plays a novel role in adipocyte differentiation.Molecular endocrinology (Baltimore, Md.) · 2013Article
- The elongation complex components BRD4 and MLLT3/AF9 are transcriptional coactivators of nuclear retinoid receptors.PloS one · 2013Article
- Article
- A prospective study of LINE-1DNA methylation and development of adiposity in school-age children.PloS one · 2013Article
- A pathway-based analysis on the effects of obstructive sleep apnea in modulating visceral fat transcriptome.Sleep · 2013Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obese patients have chronic, low-grade inflammation that predisposes to type 2 diabetes and results, in part, from dysregulated visceral white adipose tissue (WAT) functions. The specific signaling pathways underlying WAT dysregulation, however, remain unclear. Here we report that the PPARgamma signaling pathway operates differently in the visceral WAT of lean and obese mice. PPARgamma in visceral, but not subcutaneous, WAT from obese mice displayed increased sensitivity to activation by its agonist rosiglitazone. This increased sensitivity correlated with increased expression of the gene encoding the ubiquitin hydrolase/ligase ubiquitin carboxyterminal esterase L1 (UCH-L1) and with increased degradation of the PPARgamma heterodimerization partner retinoid X receptor alpha (RXRalpha), but not RXRbeta, in visceral WAT from obese humans and mice. Interestingly, increased UCH-L1 expression and RXRalpha proteasomal degradation was induced in vitro by conditions mimicking hypoxia, a condition that occurs in obese visceral WAT. Finally, PPARgamma-RXRbeta heterodimers, but not PPARgamma-RXRalpha complexes, were able to efficiently dismiss the transcriptional corepressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) upon agonist binding. Increasing the RXRalpha/RXRbeta ratio resulted in increased PPARgamma responsiveness following agonist stimulation. Thus, the selective proteasomal degradation of RXRalpha initiated by UCH-L1 upregulation modulates the relative affinity of PPARgamma heterodimers for SMRT and their responsiveness to PPARgamma agonists, ultimately activating the PPARgamma-controlled gene network in visceral WAT of obese animals and humans.
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