Leptin Signaling Modulates the Activity of Urocortin 1 Neurons in the Mouse Nonpreganglionic Edinger-Westphal Nucleus
Leptin directly modulates the activity of midbrain LepRb expressing urocortin 1 neurons by recruiting JAK-STAT signaling mediated by STAT3 phosphorylation. A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed subst...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2011-03, Vol.152 (3), p.979-988 |
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| creator | Xu, Lu Scheenen, Wim J. J. M Leshan, Rebecca L Patterson, Christa M Elias, Carol F Bouwhuis, Sanne Roubos, Eric Willem Myers, Martin G Kozicz, Tamás |
| description | Leptin directly modulates the activity of midbrain LepRb expressing urocortin 1 neurons by recruiting JAK-STAT signaling mediated by STAT3 phosphorylation.
A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed substantial LepRb mRNA expression in the nonpreganglionic Edinger-Westphal nucleus (npEW) in the rostroventral part of the midbrain. This nucleus hosts the majority of urocortin 1 (Ucn1) neurons in the rodent brain, and because Ucn1 is a potent satiety hormone and electrical lesioning of the npEW strongly decreases food intake, we have hypothesized a role of npEW-Ucn1 neurons in leptin-controlled food intake. Here, we show by immunohistochemistry that npEW-Ucn1 neurons in the mouse contain LepRb and respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivo and in vitro. Furthermore, systemic leptin administration increases the Ucn1 content of the npEW significantly, whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. Finally, we reveal by patch clamping of midbrain Ucn1 neurons that leptin administration reduces the electrical firing activity of the Ucn1 neurons. In conclusion, we provide ample evidence for leptin actions that go beyond leptin's well-known targets in the hypothalamus and propose that leptin can directly influence the activity of the midbrain Ucn1 neurons. |
| doi_str_mv | 10.1210/en.2010-1143 |
| format | Article |
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A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed substantial LepRb mRNA expression in the nonpreganglionic Edinger-Westphal nucleus (npEW) in the rostroventral part of the midbrain. This nucleus hosts the majority of urocortin 1 (Ucn1) neurons in the rodent brain, and because Ucn1 is a potent satiety hormone and electrical lesioning of the npEW strongly decreases food intake, we have hypothesized a role of npEW-Ucn1 neurons in leptin-controlled food intake. Here, we show by immunohistochemistry that npEW-Ucn1 neurons in the mouse contain LepRb and respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivo and in vitro. Furthermore, systemic leptin administration increases the Ucn1 content of the npEW significantly, whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. Finally, we reveal by patch clamping of midbrain Ucn1 neurons that leptin administration reduces the electrical firing activity of the Ucn1 neurons. In conclusion, we provide ample evidence for leptin actions that go beyond leptin's well-known targets in the hypothalamus and propose that leptin can directly influence the activity of the midbrain Ucn1 neurons.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2010-1143</identifier><identifier>PMID: 21209012</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>Animals ; Biological and medical sciences ; Brain ; Edinger-Westphal nucleus ; Firing pattern ; Food intake ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Hypothalamus ; Immunohistochemistry ; Janus kinase ; Janus kinase 2 ; Kinases ; Leptin - metabolism ; Male ; Mesencephalon ; Mesencephalon - cytology ; Mice ; Neuroendocrinology ; Neurons ; Neurons - metabolism ; Patch-Clamp Techniques ; Receptors, Leptin - genetics ; Receptors, Leptin - metabolism ; Satiety ; Signal Transduction - physiology ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - metabolism ; Urocortin ; Urocortins - genetics ; Urocortins - metabolism ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2011-03, Vol.152 (3), p.979-988</ispartof><rights>Copyright © 2011 by the Endocrine Society</rights><rights>Copyright © 2011 by the Endocrine Society 2011</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c583t-2cca67ba9b9b4eed513b2397eaee04c19b18b8a9d52abc4d17febecf90352da53</citedby><cites>FETCH-LOGICAL-c583t-2cca67ba9b9b4eed513b2397eaee04c19b18b8a9d52abc4d17febecf90352da53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23916402$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21209012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Lu</creatorcontrib><creatorcontrib>Scheenen, Wim J. J. M</creatorcontrib><creatorcontrib>Leshan, Rebecca L</creatorcontrib><creatorcontrib>Patterson, Christa M</creatorcontrib><creatorcontrib>Elias, Carol F</creatorcontrib><creatorcontrib>Bouwhuis, Sanne</creatorcontrib><creatorcontrib>Roubos, Eric Willem</creatorcontrib><creatorcontrib>Myers, Martin G</creatorcontrib><creatorcontrib>Kozicz, Tamás</creatorcontrib><title>Leptin Signaling Modulates the Activity of Urocortin 1 Neurons in the Mouse Nonpreganglionic Edinger-Westphal Nucleus</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>Leptin directly modulates the activity of midbrain LepRb expressing urocortin 1 neurons by recruiting JAK-STAT signaling mediated by STAT3 phosphorylation.
A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed substantial LepRb mRNA expression in the nonpreganglionic Edinger-Westphal nucleus (npEW) in the rostroventral part of the midbrain. This nucleus hosts the majority of urocortin 1 (Ucn1) neurons in the rodent brain, and because Ucn1 is a potent satiety hormone and electrical lesioning of the npEW strongly decreases food intake, we have hypothesized a role of npEW-Ucn1 neurons in leptin-controlled food intake. Here, we show by immunohistochemistry that npEW-Ucn1 neurons in the mouse contain LepRb and respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivo and in vitro. Furthermore, systemic leptin administration increases the Ucn1 content of the npEW significantly, whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. Finally, we reveal by patch clamping of midbrain Ucn1 neurons that leptin administration reduces the electrical firing activity of the Ucn1 neurons. In conclusion, we provide ample evidence for leptin actions that go beyond leptin's well-known targets in the hypothalamus and propose that leptin can directly influence the activity of the midbrain Ucn1 neurons.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Edinger-Westphal nucleus</subject><subject>Firing pattern</subject><subject>Food intake</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Hypothalamus</subject><subject>Immunohistochemistry</subject><subject>Janus kinase</subject><subject>Janus kinase 2</subject><subject>Kinases</subject><subject>Leptin - metabolism</subject><subject>Male</subject><subject>Mesencephalon</subject><subject>Mesencephalon - cytology</subject><subject>Mice</subject><subject>Neuroendocrinology</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Patch-Clamp Techniques</subject><subject>Receptors, Leptin - genetics</subject><subject>Receptors, Leptin - metabolism</subject><subject>Satiety</subject><subject>Signal Transduction - physiology</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Urocortin</subject><subject>Urocortins - genetics</subject><subject>Urocortins - metabolism</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFv1DAQhS0EotuFG2dkCSEupHhsZ5NckKqqBaTtcoCKo-U4k6yrrJ3aSaX-exzt0gUEJ2vkT-_Nm0fIK2BnwIF9QHfGGbAMQIonZAGVzLMCCvaULBgDkRWcFyfkNMbbNEopxXNywoGzigFfkGmNw2gd_WY7p3vrOnrtm6nXI0Y6bpGem9He2_GB-pbeBG98mGmgG5yCd5GmYcau_RSRbrwbAnbadb31zhp62SRFDNkPjOOw1T3dTKbHKb4gz1rdR3x5eJfk5ury-8XnbP3105eL83Vm8lKMGTdGr4paV3VVS8QmB1FzURWoEZk0UNVQ1qWumpzr2sgGihZrNG3FRM4bnYsl-bjXHaZ6h41BNwbdqyHYnQ4Pymur_vxxdqs6f68Ek4wluyV5dxAI_m5KKdTORoN9rx2myKrMhSyA5yKRb_4ib_0U0k2jEiDYCspS8ES931Mm-BgDto-7AFNznQqdmutUc50Jf_37_o_wr_4S8PYA6Gh03wbtjI1HTlSwkowfc_hp-J9ldrAUexJd402wDlOlMR7T_HPRn96Ax4I</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Xu, Lu</creator><creator>Scheenen, Wim J. 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Psychology</topic><topic>Gene Expression</topic><topic>Hypothalamus</topic><topic>Immunohistochemistry</topic><topic>Janus kinase</topic><topic>Janus kinase 2</topic><topic>Kinases</topic><topic>Leptin - metabolism</topic><topic>Male</topic><topic>Mesencephalon</topic><topic>Mesencephalon - cytology</topic><topic>Mice</topic><topic>Neuroendocrinology</topic><topic>Neurons</topic><topic>Neurons - metabolism</topic><topic>Patch-Clamp Techniques</topic><topic>Receptors, Leptin - genetics</topic><topic>Receptors, Leptin - metabolism</topic><topic>Satiety</topic><topic>Signal Transduction - physiology</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Urocortin</topic><topic>Urocortins - genetics</topic><topic>Urocortins - metabolism</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Lu</creatorcontrib><creatorcontrib>Scheenen, Wim J. 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J. M</au><au>Leshan, Rebecca L</au><au>Patterson, Christa M</au><au>Elias, Carol F</au><au>Bouwhuis, Sanne</au><au>Roubos, Eric Willem</au><au>Myers, Martin G</au><au>Kozicz, Tamás</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leptin Signaling Modulates the Activity of Urocortin 1 Neurons in the Mouse Nonpreganglionic Edinger-Westphal Nucleus</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>152</volume><issue>3</issue><spage>979</spage><epage>988</epage><pages>979-988</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>Leptin directly modulates the activity of midbrain LepRb expressing urocortin 1 neurons by recruiting JAK-STAT signaling mediated by STAT3 phosphorylation.
A recent study systematically characterized the distribution of the long form of the leptin receptor (LepRb) in the mouse brain and showed substantial LepRb mRNA expression in the nonpreganglionic Edinger-Westphal nucleus (npEW) in the rostroventral part of the midbrain. This nucleus hosts the majority of urocortin 1 (Ucn1) neurons in the rodent brain, and because Ucn1 is a potent satiety hormone and electrical lesioning of the npEW strongly decreases food intake, we have hypothesized a role of npEW-Ucn1 neurons in leptin-controlled food intake. Here, we show by immunohistochemistry that npEW-Ucn1 neurons in the mouse contain LepRb and respond to leptin administration with induction of the Janus kinase 2-signal transducer and activator of transcription 3 pathway, both in vivo and in vitro. Furthermore, systemic leptin administration increases the Ucn1 content of the npEW significantly, whereas in mice that lack LepRb (db/db mice), the npEW contains considerably reduced amount of Ucn1. Finally, we reveal by patch clamping of midbrain Ucn1 neurons that leptin administration reduces the electrical firing activity of the Ucn1 neurons. In conclusion, we provide ample evidence for leptin actions that go beyond leptin's well-known targets in the hypothalamus and propose that leptin can directly influence the activity of the midbrain Ucn1 neurons.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>21209012</pmid><doi>10.1210/en.2010-1143</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Brain Edinger-Westphal nucleus Firing pattern Food intake Fundamental and applied biological sciences. Psychology Gene Expression Hypothalamus Immunohistochemistry Janus kinase Janus kinase 2 Kinases Leptin - metabolism Male Mesencephalon Mesencephalon - cytology Mice Neuroendocrinology Neurons Neurons - metabolism Patch-Clamp Techniques Receptors, Leptin - genetics Receptors, Leptin - metabolism Satiety Signal Transduction - physiology STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Urocortin Urocortins - genetics Urocortins - metabolism Vertebrates: endocrinology |
| title | Leptin Signaling Modulates the Activity of Urocortin 1 Neurons in the Mouse Nonpreganglionic Edinger-Westphal Nucleus |
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