title: Prolactin potentiates insulin-stimulated leptin expression and release from differentiated brown adipocytes.
abstract: The pituitary hormone prolactin (PRL) exerts pleiotropic effects, which are mediated by a membrane receptor (PRLR) present in numerous cell types including adipocytes. Brown adipose tissue (BAT) expresses uncoupling proteins (UCPs), involved in thermogenesis, but also secretes leptin, a key hormone involved in the control of body weight. To investigate PRL effects on BAT, we used the T37i brown adipose cell line, and demonstrated that PRLRs are expressed as a function of cell differentiation. Addition of PRL leads to activation of the JAK/STAT and MAP kinase signaling pathways, demonstrating that PRLRs are functional in these cells. Basal and catecholamine-induced UCP1 expression were not affected by PRL. However, PRL combined with insulin significantly increases leptin expression and release, indicating that PRL potentiates the stimulatory effect of insulin as revealed by the recruitment of insulin receptor substrates and the activation of phosphatidylinositol 3-kinase. To explore the in vivo physiological relevance of PRL action in BAT, we showed that leptin content was significantly increased in BAT of PRLR-null mice compared with wild-type mice, highlighting the involvement of PRL in the leptin secretion process. This study provides the first evidence for a functional link between PRL and energy balance via a cross-talk between insulin and PRL signaling pathways in brown adipocytes.
authors.affiliation: INSERM U478, Institut Fédératif de Recherche Claude Bernard, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Viengchareun
authors.forename: H
authors.initials: H
authors.lastname: Bouzinba-Segard
authors.forename: J-P
authors.initials: JP
authors.lastname: Laigneau
authors.forename: M-C
authors.initials: MC
authors.lastname: Zennaro
authors.forename: P A
authors.initials: PA
authors.lastname: Kelly
authors.forename: A
authors.initials: A
authors.lastname: Bado
authors.forename: M
authors.initials: M
authors.lastname: Lombès
authors.forename: N
authors.initials: N
authors.lastname: Binart
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007473:Ion Channels; D053614:Janus Kinase 2; D020738:Leptin / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D054411:Receptors, Leptin; D011981:Receptors, Prolactin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D000071256:Uncoupling Protein 1
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D008894:Milk Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D054411:Receptors, Leptin; D011981:Receptors, Prolactin; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C515447:leptin receptor, mouse; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D020928:Mitogen-Activated Protein Kinases