title: Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling.
abstract: BACKGROUND
  Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT).
  
  
  RESULTS
  We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and metabolism within the first two weeks of postnatal life consistent with the expected transition from BAT to WAT. The transformation was characterized by massively decreased mitochondrial abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose and the transition phase 170 genes were differentially expressed, and 717 genes were differentially expressed between the transition and the white adipose phase. Thirty-eight genes were shared among the two sets of differentially expressed genes. We identified a number of regulated transcription factors, including NR1H3, MYC, KLF4, ESR1, RELA and BCL6, which were linked to the overall changes in gene expression during the adipose tissue remodeling. Finally, the perirenal adipose tissue expressed both brown and brite/beige adipocyte marker genes at birth, the expression of which changed substantially over time.
  
  
  CONCLUSIONS
  Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides a useful resource for further studies in adipose tissue plasticity.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. astrid.basse@bio.ku.dk.|Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. astrid.basse@bio.ku.dk.
authors.forename: Astrid L
authors.initials: AL
authors.lastname: Basse
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. dixen.karen@gmail.com.|Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. dixen.karen@gmail.com.
authors.forename: Karen
authors.initials: K
authors.lastname: Dixen
authors.affiliation: Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark. rachita@cbs.dtu.dk.|Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. rachita@cbs.dtu.dk.
authors.forename: Rachita
authors.initials: R
authors.lastname: Yadav
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, DK-1870, Frederiksberg, Denmark. mpt@stevnslam.dk.
authors.forename: Malin P
authors.initials: MP
authors.lastname: Tygesen
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. qvortrup@sund.ku.dk.
authors.forename: Klaus
authors.initials: K
authors.lastname: Qvortrup
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. karsten.kristiansen@bio.ku.dk.
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. bqui@sund.ku.dk.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Quistorff
authors.affiliation: Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark. ramneek@cbs.dtu.dk.
authors.forename: Ramneek
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. wangj@genomics.org.cn.|BGI-Shenzhen, Shenzhen, 518083, China. wangj@genomics.org.cn.|Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah, 21589, Saudi Arabia. wangj@genomics.org.cn.|Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, 999078, China. wangj@genomics.org.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Systems Biology, Center for Biological Sequence Analysis, Technical University of Denmark, DK-2800, Kongens Lyngby, Denmark. jacob.hansen@bio.ku.dk.
authors.forename: Jacob B
authors.initials: JB
authors.lastname: Hansen
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D016000:Cluster Analysis; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D025341:Principal Component Analysis; D012756:Sheep / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D004272:DNA, Mitochondrial; D007473:Ion Channels; D024101:Mitochondrial Proteins; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; D002950:Citrate (si)-Synthase