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dc.contributor.author Viengchareun, S
dc.contributor.author Servel, N
dc.contributor.author Fève, B
dc.contributor.author Freemark, M
dc.contributor.author Lombès, M
dc.contributor.author Binart, N
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:22Z
dc.date.issued 2008
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/18253483
dc.identifier.citation PLoS One, 2008, 3 (2), pp. e1535 - ?
dc.identifier.uri http://hdl.handle.net/10161/4483
dc.description.abstract BACKGROUND: The lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding to PRL receptor (PRLR), highly expressed in brown adipose tissue (BAT), yet their impact on adipocyte function and metabolism remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: PRLR knockout (KO) newborn mice were phenotypically characterized in terms of thermoregulation and their BAT differentiation assayed for gene expression studies. Derived brown preadipocyte cell lines were established to evaluate the molecular mechanisms involved in PRL signaling on BAT function. Here, we report that newborn mice lacking PRLR have hypotrophic BAT depots that express low levels of adipocyte nuclear receptor PPARgamma2, its coactivator PGC-1alpha, uncoupling protein 1 (UCP1) and the beta3 adrenoceptor, reducing mouse viability during cold challenge. Immortalized PRLR KO preadipocytes fail to undergo differentiation into mature adipocytes, a defect reversed by reintroduction of PRLR. That the effects of the lactogens in BAT are at least partly mediated by Insulin-like Growth Factor-2 (IGF-2) is supported by: i) a striking reduction in BAT IGF-2 expression in PRLR KO mice and in PRLR-deficient preadipocytes; ii) induction of cellular IGF-2 expression by PRL through JAK2/STAT5 pathway activation; and iii) reversal of defective differentiation in PRLR KO cells by exogenous IGF-2. CONCLUSIONS: Our findings demonstrate that the lactogens act in concert with IGF-2 to control brown adipocyte differentiation and growth. Given the prominent role of brown adipose tissue during the perinatal period, our results identified prolactin receptor signaling as a major player and a potential therapeutic target in protecting newborn mammals against hypothermia.
dc.format.extent e1535 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0001535
dc.subject Adaptation, Physiological
dc.subject Adipocytes, Brown
dc.subject Animals
dc.subject Animals, Newborn
dc.subject Cell Differentiation
dc.subject Cold Temperature
dc.subject Gene Expression Regulation
dc.subject Insulin-Like Growth Factor II
dc.subject Mice
dc.subject Mice, Knockout
dc.subject Phenotype
dc.subject Receptors, Prolactin
dc.subject Signal Transduction
dc.title Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2008-2-6 en_US
duke.description.endpage e1535 en_US
duke.description.issue 2 en_US
duke.description.startpage e1535 en_US
duke.description.volume 3 en_US
dc.relation.journal Plos One en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/18253483
pubs.issue 2
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Pediatrics/Pediatrics, Endocrinology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Molecular Physiology Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Molecular Physiology Institute/Sarah Stedman Nutrition & Metabolism Center
pubs.volume 3
dc.identifier.eissn 1932-6203

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