title: Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice.
abstract: Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a "brite" transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with "browning," as these represent novel targets for understanding this process. For example, neuregulin 4 was more highly expressed in brown adipose tissue and upregulated in white fat upon cold exposure, and cell studies showed that it is a neurite outgrowth-promoting adipokine, indicative of a role in increasing adipose tissue innervation in response to cold. A cell culture system that allows us to reproduce the differential properties of the discrete adipose depots was developed to study depot-specific differences at an in vitro level. The key transcriptional events underpinning white adipose tissue to brown transition are important, as they represent an attractive proposition to overcome the detrimental effects associated with metabolic disorders, including obesity and type 2 diabetes.
authors.affiliation: Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College London, London, United Kingdom;
authors.forename: Meritxell
authors.initials: M
authors.lastname: Rosell
authors.forename: Myrsini
authors.initials: M
authors.lastname: Kaforou
authors.forename: Andrea
authors.initials: A
authors.lastname: Frontini
authors.forename: Anthony
authors.initials: A
authors.lastname: Okolo
authors.forename: Yi-Wah
authors.initials: YW
authors.lastname: Chan
authors.forename: Evanthia
authors.initials: E
authors.lastname: Nikolopoulou
authors.forename: Steven
authors.initials: S
authors.lastname: Millership
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Fenech
authors.forename: David
authors.initials: D
authors.lastname: MacIntyre
authors.forename: Jeremy O
authors.initials: JO
authors.lastname: Turner
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Moore
authors.forename: Edith
authors.initials: E
authors.lastname: Blackburn
authors.forename: William J
authors.initials: WJ
authors.lastname: Gullick
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montana
authors.forename: Malcolm G
authors.initials: MG
authors.lastname: Parker
authors.forename: Mark
authors.initials: M
authors.lastname: Christian
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D058639:Cold-Shock Response / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D016716:PC12 Cells; D051381:Rats; D059467:Transcriptome
keywords: adipokine; brite; brown adipose tissue; cold; subcutaneous white adipose tissue; visceral white adipose tissue