Cited time in webofscience Cited time in scopus

ROR alpha controls hepatic lipid homeostasis via negative regulation of PPAR gamma transcriptional network

Title
ROR alpha controls hepatic lipid homeostasis via negative regulation of PPAR gamma transcriptional network
Author(s)
Kim, KyeongkyuBoo, KyungjinYu, Young SukOh, Se KyuKim, HyunkyungJeon, YoonBhin, JinhyukHwang, DaeheeKim, Keun IlLee, Jun-SuIm, Seung-SoonYoon, Seul GiKim, Il YongSeong, Je KyungLee, HoFang, SungsoonBaek, Sung Hee
Issued Date
2017-07
Citation
Nature Communications, v.8, no.1
Type
Article
Keywords
Diet Induced ObesityExpressionFatty LiverInsulin ResistanceLarge Gene ListsMetabolic SyndromeMusOrphan Nuclear ReceptorsRev ErbRNA SeqStaggerer Mouse
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).
URI
http://hdl.handle.net/20.500.11750/4447
DOI
10.1038/s41467-017-00215-1
Publisher
Nature Publishing Group
Files in This Item:
10.1038_s41467_017_00215_1.pdf

10.1038_s41467_017_00215_1.pdf

기타 데이터 / 1.89 MB / Adobe PDF download
Appears in Collections:
Department of New Biology Systems Biology and Medicine Lab 1. Journal Articles

qrcode

  • twitter
  • facebook
  • mendeley

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE