RNF20 Functions as a Transcriptional Coactivator for PPARγ by Promoting NCoR1 Degradation in Adipocytes
| Autor: | Dabin Lee, Lee Jaeho, Yong Geun Jeon, Seul Gi Yoon, Dong Wook Kim, Jeu Park, Sung Sik Choe, Je-Yoel Cho, Kyung Cheul Shin, Je Kyung Seong, Jee Hyung Sohn, Yul Ji, Jae Bum Kim |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Endocrinology Diabetes and Metabolism Ubiquitin-Protein Ligases Adipose tissue Mice Obese 030209 endocrinology & metabolism Mice Transgenic Diet High-Fat 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Adipocyte Internal Medicine Adipocytes Animals Humans Nuclear Receptor Co-Repressor 1 Obesity Receptor Nuclear receptor co-repressor 1 Chemistry Wild type Lipid metabolism Cell biology Mice Inbred C57BL PPAR gamma 030104 developmental biology HEK293 Cells Adipogenesis Proteolysis Trans-Activators Corepressor |
| Zdroj: | Diabetes. 69(1) |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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