title: MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes.
abstract: Brown adipose tissue (BAT) is specialized to burn lipids for heat generation as a natural defense against cold and obesity. Previous studies established microRNAs (miRNAs) as essential regulators of brown adipocyte differentiation, but whether miRNAs are required for the feature maintenance of mature brown adipocytes remains unknown. To address this question, we ablated Dgcr8, a key regulator of the miRNA biogenesis pathway, in mature brown as well as in white adipocytes. Adipose tissue-specific Dgcr8 knockout mice displayed enlarged but pale interscapular brown fat with decreased expression of genes characteristic of brown fat and were intolerant to cold exposure. Primary brown adipocyte cultures in vitro confirmed that miRNAs are required for marker gene expression in mature brown adipocytes. We also demonstrated that miRNAs are essential for the browning of subcutaneous white adipocytes in vitro and in vivo. Using this animal model, we performed miRNA expression profiling analysis and identified a set of BAT-specific miRNAs that are upregulated during brown adipocyte differentiation and enriched in brown fat compared with other organs. We identified miR-182 and miR-203 as new regulators of brown adipocyte development. Taken together, our study demonstrates an essential role of miRNAs in the maintenance as well as in the differentiation of brown adipocytes.
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Hyunjii
authors.initials: H
authors.lastname: Cho
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Alexander
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: Heide Christine
authors.initials: HC
authors.lastname: Patterson
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Minxia
authors.initials: M
authors.lastname: Gu
authors.affiliation: Institute of Molecular and Cell Biology, Singapore.
authors.forename: Kinyui Alice
authors.initials: KA
authors.lastname: Lo
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Goh
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Long N
authors.initials: LN
authors.lastname: Nguyen
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Chai
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Cher X
authors.initials: CX
authors.lastname: Huang
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Kovalik
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: Sujoy
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: University of Geneva, Medical Faculty, Department of Cell Physiology and Metabolism, Centre Médical Universitaire (CMU), Geneva, Switzerland.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trajkovski
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore.
authors.forename: David L
authors.initials: DL
authors.lastname: Silver
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA.
authors.forename: Harvey
authors.initials: H
authors.lastname: Lodish
authors.affiliation: Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Graduate Medical School, Singapore Institute of Molecular and Cell Biology, Singapore sun.lei@duke-nus.edu.sg.
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D052438:Adipocytes, White / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D016601:RNA-Binding Proteins / Q000235:genetics
chemical_list: C474044:Dgcr8 protein, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D016601:RNA-Binding Proteins