دورية أكاديمية
ROR慣 controls hepatic lipid homeostasis via negative regulation of PPAR款 transcriptional network.
| العنوان: | ROR慣 controls hepatic lipid homeostasis via negative regulation of PPAR款 transcriptional network. |
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| المساهمون: | College of Medicine, Dept. of Life Science, Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Se Kyu Oh, Hyunkyung Kim, Yoon Jeon, Jinhyuk Bhin, Daehee Hwang, Keun Il Kim, Jun-Su Lee, Seung-Soon Im, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Ho Lee, Sungsoon Fang, Sung Hee Baek, Fang, Sungsoon |
| بيانات النشر: | Nature Pub. Group |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Animals, Diet, High-Fat, Fatty Liver/genetics, Gene Expression Regulation/genetics, Gene Regulatory Networks, Glucose/metabolism, Histone Deacetylases/metabolism, Homeostasis, Insulin Resistance/genetics, Lipid Metabolism/genetics, Lipogenesis/genetics, Liver/metabolism, Mice, Nuclear Receptor Subfamily 1, Group F, Member 1/genetics, Obesity/genetics, PPAR gamma/antagonists & inhibitors, PPAR gamma/genetics, Promoter Regions, Genetic/genetics |
| الوصف: | The retinoic acid receptor-related orphan receptor-慣 (ROR慣) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic ROR慣 controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-款 (PPAR款) that mediates hepatic lipid metabolism. Liver-specific Ror慣-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD). Global transcriptome analysis reveals that liver-specific deletion of Ror慣 leads to the dysregulation of PPAR款 signaling and increases hepatic glucose and lipid metabolism. ROR慣 specifically binds and recruits histone deacetylase 3 (HDAC3) to PPAR款 target promoters for the transcriptional repression of PPAR款. PPAR款 antagonism restores metabolic homeostasis in HFD-fed liver-specific Ror慣 deficient mice. Our data indicate that ROR慣 has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic strategies designed to modulate ROR慣 activity may be beneficial for the treatment of metabolic disorders.Hepatic steatosis development may result from dysregulation of lipid metabolism, which is finely tuned by several transcription factors including the PPAR family. Here Kim et al. show that the nuclear receptor ROR慣 inhibits PPAR款-mediated transcriptional activity by interacting with HDAC3 and competing for the promoters of lipogenic genes. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | NATURE COMMUNICATIONS; J02293; OAK-2017-03891; https://ir.ymlib.yonsei.ac.kr/handle/22282913/160522Test; T201702567; NATURE COMMUNICATIONS, Vol.8(162) : 1-15, 2017 |
| DOI: | 10.1038/s41467-017-00215-1 |
| الإتاحة: | https://doi.org/10.1038/s41467-017-00215-1Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/160522Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.AD2619CD |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-017-00215-1 |