De Novo Reconstruction of Adipose Tissue Transcriptomes Reveals Long Non-coding RNA Regulators of Brown Adipocyte Development

• Main Authors: Bai, Zhiqiang (Author), Xu, Dan (Author), Yuan, Bingbing (Author), Lo, Kinyui Alice (Author), Yoon, Myeong Jin (Author), Lim, Yen Ching (Author), Knoll, Marko (Author), Chen, Shuai (Author), Chen, Peng (Author), Sun, Lei (Author), Alvarez, Juan Rene (Contributor), Slavov, Nikolai G (Contributor), Lodish, Harvey F (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Whitehead Institute for Biomedical Research (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2016-12-13T15:00:06Z.
• Subjects: Article
• Online Access: Get fulltext

Brown adipose tissue (BAT) protects against obesity by promoting energy expenditure via uncoupled respiration. To uncover BAT-specific long non-coding RNAs (lncRNAs), we used RNA-seq to reconstruct de novo transcriptomes of mouse brown, inguinal white, and epididymal white fat and identified ∼1,500 lncRNAs, including 127 BAT-restricted loci induced during differentiation and often targeted by key regulators PPARγ, C/EBPα, and C/EBPβ. One of them, lnc-BATE1, is required for establishment and maintenance of BAT identity and thermogenic capacity. lnc-BATE1 inhibition impairs concurrent activation of brown fat and repression of white fat genes and is partially rescued by exogenous lnc-BATE1 with mutated siRNA-targeting sites, demonstrating a function in trans. We show that lnc-BATE1 binds heterogeneous nuclear ribonucleoprotein U and that both are required for brown adipogenesis. Our work provides an annotated catalog for the study of fat depot-selective lncRNAs and establishes lnc-BATE1 as a regulator of BAT development and physiology.
National Institutes of Health (U.S.) (Grants DK047618, DK068348 and 5P01 HL066105)
Singapore. Ministry of Health (Singapore National Research Foundation. CBRG Grant NMRC/CBRG/0070/2014)