|
RORα controls hepatic lipid homeostasis via negative regulation of PPARγ transcriptional network
 Authors and Affiliations  Authors and Affiliations
Kyeongkyu Kim1, Kyungjin Boo1, Young Suk Yu1, Se Kyu Oh1, Hyunkyung Kim1, Yoon Jeon2, Jinhyuk Bhin3, Daehee Hwang3, Keun Il Kim4, Jun-Su Lee5, Seung-Soon Im5, Seul Gi Yoon6,7, Il Yong Kim6,7, Je Kyung Seong6,7,8, Ho Lee2, Sungsoon Fang9,* & Sung Hee Baek1,*
1Department of Biological Sciences, Creative Research Initiatives Center for Chromatin Dynamics, Seoul National University, Seoul 08826, South Korea. 2Graduate School of Cancer Science and Policy, Research Institute, National Cancer Center, Gyeonggi-do 10408, South Korea. 3Department of New Biology and Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 42988, South Korea. 4Department of Biological Sciences, Sookmyung Women’s University, Seoul 04310, South Korea. 5Department of Physiology, Keimyung University School of Medicine, Daegu 42601, South Korea. 6 Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea. 7 Korea Mouse Phenotyping Center, Seoul 08826, South Korea. 8 BK21 Plus Program for Creative Veterinary Science Research, BIO-MAX institute, Interdisciplinary Program for Bioinformatics and Program for Cancer Biology, Seoul National University, Seoul 08826, South Korea. 9 Severance Biomedical Science Institute, BK21 Plus Project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, South Korea.
Kyeongkyu Kim and Kyungjin Boo contributed equally to this work.
*Correspondence to Sungsoon Fang or Sung Hee Baek
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.
|
e브릭몰 
김경규 (서울대학교)
Google (by Sung Hee Baek)
Pubmed (by Sung Hee Baek)
![[웨비나]Spatial Genomic 연구: nanoString GeoMx DSP Webex에 초대합니다.](/upload/board/files/bioschedule_pri/pri_0247293.jpg)
