2. Academic Validation
  3. Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators

Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators

  • PLoS Biol. 2017 Aug 1;15(8):e2002176. doi: 10.1371/journal.pbio.2002176.
Zhiqiang Bai 1 2,  Xiao-Ran Chai 1,  Myeong Jin Yoon 1,  Hye-Jin Kim 1,  Kinyui Alice Lo 1 3,  Zhi-Chun Zhang 1,  Dan Xu 1,  Diana Teh Chee Siang 1,  Arcinas Camille Esther Walet 1,  Shao-Hai Xu 4,  Sook-Yoong Chia 1,  Peng Chen 4,  Hongyuan Yang 5,  Sujoy Ghosh 1,  Lei Sun 1 3
Affiliations

Affiliations

  • 1 Cardiovascular and Metabolic Disorders Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
  • 2 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
  • 3 Institute of Molecular and Cell Biology, Singapore, Singapore.
  • 4 Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.
  • 5 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
PMID: 28763438 DOI: 10.1371/journal.pbio.2002176
Abstract

Enhancing brown fat activity and promoting white fat browning are attractive therapeutic strategies for treating obesity and associated metabolic disorders. To provide a comprehensive picture of the gene regulatory network in these processes, we conducted a series of transcriptome studies by RNA Sequencing (RNA-seq) and quantified the mRNA and long noncoding RNA (lncRNA) changes during white fat browning (chronic cold exposure, beta-adrenergic agonist treatment, and intense exercise) and brown fat activation or inactivation (acute cold exposure or thermoneutrality, respectively). mRNA-lncRNA coexpression networks revealed dynamically regulated lncRNAs to be largely embedded in nutrient and energy metabolism pathways. We identified a brown adipose tissue-enriched lncRNA, lncBATE10, that was governed by the cAMP-cAMP response element-binding protein (Creb) axis and required for a full brown fat differentiation and white fat browning program. Mechanistically, lncBATE10 can decoy Celf1 from Pgc1α, thereby protecting Pgc1α mRNA from repression by Celf1. Together, these studies provide a comprehensive data framework to interrogate the transcriptomic changes accompanying energy homeostasis transition in adipose tissue.

Figures