RNF20 Functions as a Transcriptional Coactivator for PPARγ by Promoting NCoR1 Degradation in Adipocytes
Open Access
- 11 October 2019
- journal article
- research article
- Published by American Diabetes Association in Diabetes
- Vol. 69 (1), 20-34
- https://doi.org/10.2337/db19-0508
Abstract
Adipose tissue is the key organ coordinating whole-body energy homeostasis. Although it has been reported that ring finger protein 20 (RNF20) regulates lipid metabolism in the liver and kidney, the roles of RNF20 in adipose tissue have not been explored. Here, we demonstrate that RNF20 promotes adipogenesis by potentiating the transcriptional activity of peroxisome proliferator–activated receptor-γ (PPARγ). Under normal chow diet feeding, Rnf20 defective (Rnf20+/−) mice exhibited reduced fat mass with smaller adipocytes compared with wild-type littermates. In addition, high-fat diet–fed Rnf20+/− mice alleviated systemic insulin resistance accompanied by a reduced expansion of fat tissue. Quantitative proteomic analyses revealed significantly decreased levels of PPARγ target proteins in adipose tissue of Rnf20+/− mice. Mechanistically, RNF20 promoted proteasomal degradation of nuclear corepressor 1 (NCoR1), which led to stimulation of the transcriptional activity of PPARγ. Collectively, these data suggest that RNF20-NCoR1 is a novel axis in adipocyte biology through fine-tuning the transcriptional activity of PPARγ.Keywords
Funding Information
- the National Creative Research Initiative Program of the National Research Foundation of Korea (Ministry of Science and ICT (2011-0018312)
- the Korea Mouse Phenotyping Project of the National Research Foundation of Korea (2014M3A9D5A01073598, 2013M3A9D5072550)
- the BK21 Plus program (21A20131212006)
This publication has 50 references indexed in Scilit:
- Emerging roles of the corepressors NCoR1 and SMRT in homeostasisGenes & Development, 2013
- A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20Nature Medicine, 2012
- Adipocyte NCoR Knockout Decreases PPARγ Phosphorylation and Enhances PPARγ Activity and Insulin SensitivityCell, 2011
- Adipose tissue remodeling and obesityJCI Insight, 2011
- Epigenetic codes of PPARγ in metabolic diseaseFEBS Letters, 2011
- Extensive chromatin remodelling and establishment of transcription factor ‘hotspots’ during early adipogenesisThe EMBO Journal, 2011
- Lipodystrophy: pathophysiology and advances in treatmentNature Reviews Endocrinology, 2010
- MED14 Tethers Mediator to the N-Terminal Domain of Peroxisome Proliferator-Activated Receptor γ and Is Required for Full Transcriptional Activity and AdipogenesisMolecular and Cellular Biology, 2010
- Fat and Beyond: The Diverse Biology of PPARγAnnual Review of Biochemistry, 2008
- Regulation of Lipolysis in AdipocytesAnnual Review of Nutrition, 2007