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dc.contributor.author Kim, Kyeongkyu -
dc.contributor.author Boo, Kyungjin -
dc.contributor.author Yu, Young Suk -
dc.contributor.author Oh, Se Kyu -
dc.contributor.author Kim, Hyunkyung -
dc.contributor.author Jeon, Yoon -
dc.contributor.author Bhin, Jinhyuk -
dc.contributor.author Hwang, Daehee -
dc.contributor.author Kim, Keun Il -
dc.contributor.author Lee, Jun-Su -
dc.contributor.author Im, Seung-Soon -
dc.contributor.author Yoon, Seul Gi -
dc.contributor.author Kim, Il Yong -
dc.contributor.author Seong, Je Kyung -
dc.contributor.author Lee, Ho -
dc.contributor.author Fang, Sungsoon -
dc.contributor.author Baek, Sung Hee -
dc.date.available 2017-09-11T09:28:00Z -
dc.date.created 2017-09-11 -
dc.date.issued 2017-07 -
dc.identifier.issn 2041-1723 -
dc.identifier.uri http://hdl.handle.net/20.500.11750/4447 -
dc.description.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). -
dc.language English -
dc.publisher Nature Publishing Group -
dc.title ROR alpha controls hepatic lipid homeostasis via negative regulation of PPAR gamma transcriptional network -
dc.type Article -
dc.identifier.doi 10.1038/s41467-017-00215-1 -
dc.identifier.scopusid 2-s2.0-85026528725 -
dc.identifier.bibliographicCitation Nature Communications, v.8, no.1 -
dc.description.isOpenAccess FALSE -
dc.subject.keywordPlus Diet Induced Obesity -
dc.subject.keywordPlus Expression -
dc.subject.keywordPlus Fatty Liver -
dc.subject.keywordPlus Insulin Resistance -
dc.subject.keywordPlus Large Gene Lists -
dc.subject.keywordPlus Metabolic Syndrome -
dc.subject.keywordPlus Mus -
dc.subject.keywordPlus Orphan Nuclear Receptors -
dc.subject.keywordPlus Rev Erb -
dc.subject.keywordPlus RNA Seq -
dc.subject.keywordPlus Staggerer Mouse -
dc.citation.number 1 -
dc.citation.title Nature Communications -
dc.citation.volume 8 -
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Department of New Biology Systems Biology and Medicine Lab 1. Journal Articles

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