RORα controls hepatic lipid homeostasis via negative regulation of PPARγ transcriptional networkopen access
- Authors
- Kim K.; Boo K.; Yu Y.S.; Oh S.K.; Kim H.; Jeon Y.; Bhin J.; Hwang D.; Kim K.I.; Lee J.-S.; Im S.-S.; Yoon S.G.; Kim I.Y.; Seong J.K.; Lee H.; Fang S.; Baek S.H.
- Issue Date
- Jul-2017
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, v.8, no.1
- Indexed
- SCI
SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 8
- Number
- 1
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/5658
- DOI
- 10.1038/s41467-017-00215-1
- ISSN
- 2041-1723
- Abstract
- The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-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 Rorα leads to the dysregulation of PPARγ signaling and increases hepatic glucose and lipid metabolism. RORα specifically binds and recruits histone deacetylase 3 (HDAC3) to PPARγ target promoters for the transcriptional repression of PPARγ. PPARγ antagonism restores metabolic homeostasis in HFD-fed liver-specific Rorα deficient mice. Our data indicate that RORα has a pivotal role in the regulation of hepatic lipid homeostasis. Therapeutic strategies designed to modulate RORα activity may be beneficial for the treatment of metabolic disorders. © 2017 The Author(s).
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- Appears in
Collections - 1. Basic Science > Department of Biochemistry and Molecular Biology > 1. Journal Articles
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