MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus
Significance Both in rodents and humans, melanocortin-4 receptors (MC4Rs) suppress appetite and prevent obesity. Unfortunately, the underlying neural mechanisms by which MC4Rs regulate food intake are poorly understood. Unraveling these mechanisms may open up avenues for treating obesity. In the pre...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2014-09, Vol.111 (36), p.13193-13198 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Shah, Bhavik P. Vong, Linh Olson, David P. Koda, Shuichi Krashes, Michael J. Ye, Chianping Yang, Zongfang Fuller, Patrick M. Elmquist, Joel K. Lowell, Bradford B. |
| description | Significance Both in rodents and humans, melanocortin-4 receptors (MC4Rs) suppress appetite and prevent obesity. Unfortunately, the underlying neural mechanisms by which MC4Rs regulate food intake are poorly understood. Unraveling these mechanisms may open up avenues for treating obesity. In the present study we have established that MC4Rs on neurons in the paraventricular nucleus of the hypothalamus are both necessary and sufficient for MC4R control of feeding and that these neurons are glutamatergic and not GABAergic and do not express the neuropeptides oxytocin, corticotropin-releasing hormone, prodynorphin, or vasopressin. In addition, we identify downstream projections from these glutamatergic neurons to the lateral parabrachial nucleus, which could mediate the appetite suppressing effects. |
| doi_str_mv | 10.1073/pnas.1407843111 |
| format | Article |
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Unfortunately, the underlying neural mechanisms by which MC4Rs regulate food intake are poorly understood. Unraveling these mechanisms may open up avenues for treating obesity. In the present study we have established that MC4Rs on neurons in the paraventricular nucleus of the hypothalamus are both necessary and sufficient for MC4R control of feeding and that these neurons are glutamatergic and not GABAergic and do not express the neuropeptides oxytocin, corticotropin-releasing hormone, prodynorphin, or vasopressin. In addition, we identify downstream projections from these glutamatergic neurons to the lateral parabrachial nucleus, which could mediate the appetite suppressing effects.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1407843111</identifier><identifier>PMID: 25157144</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; appetite ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological Sciences ; Body Weight ; Brain ; corticotropin-releasing hormone ; Dependovirus - metabolism ; Energy Metabolism ; Feeding Behavior ; Food intake ; GABAergic Neurons - metabolism ; Gene Deletion ; Gene expression ; Glutamates - metabolism ; Hormones ; humans ; Hyperphagia ; Injections ; Integrases - metabolism ; Mass ; Melanocortins ; Mice ; Neurons ; Neurons - metabolism ; Neuropeptides - metabolism ; Obesity ; oxytocin ; Parabrachial Nucleus - metabolism ; paraventricular hypothalamic nucleus ; Paraventricular Hypothalamic Nucleus - metabolism ; Receptor, Melanocortin, Type 4 - metabolism ; Receptors ; Repressor Proteins - metabolism ; Reproducibility of Results ; rodents ; Satiety ; Stereotaxic Techniques ; Synapses - metabolism ; vasopressin ; Vesicular Glutamate Transport Protein 2 - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2014-09, Vol.111 (36), p.13193-13198</ispartof><rights>copyright © 1993–2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Sep 9, 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-aa3a11d404e6f26283164209fcf38fe062a5493a106e874bed1bf37a1c6b82143</citedby><cites>FETCH-LOGICAL-c624t-aa3a11d404e6f26283164209fcf38fe062a5493a106e874bed1bf37a1c6b82143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/111/36.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/43043303$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/43043303$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25157144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shah, Bhavik P.</creatorcontrib><creatorcontrib>Vong, Linh</creatorcontrib><creatorcontrib>Olson, David P.</creatorcontrib><creatorcontrib>Koda, Shuichi</creatorcontrib><creatorcontrib>Krashes, Michael J.</creatorcontrib><creatorcontrib>Ye, Chianping</creatorcontrib><creatorcontrib>Yang, Zongfang</creatorcontrib><creatorcontrib>Fuller, Patrick M.</creatorcontrib><creatorcontrib>Elmquist, Joel K.</creatorcontrib><creatorcontrib>Lowell, Bradford B.</creatorcontrib><title>MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Significance Both in rodents and humans, melanocortin-4 receptors (MC4Rs) suppress appetite and prevent obesity. Unfortunately, the underlying neural mechanisms by which MC4Rs regulate food intake are poorly understood. Unraveling these mechanisms may open up avenues for treating obesity. In the present study we have established that MC4Rs on neurons in the paraventricular nucleus of the hypothalamus are both necessary and sufficient for MC4R control of feeding and that these neurons are glutamatergic and not GABAergic and do not express the neuropeptides oxytocin, corticotropin-releasing hormone, prodynorphin, or vasopressin. In addition, we identify downstream projections from these glutamatergic neurons to the lateral parabrachial nucleus, which could mediate the appetite suppressing effects.</description><subject>Animals</subject><subject>appetite</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biological Sciences</subject><subject>Body Weight</subject><subject>Brain</subject><subject>corticotropin-releasing hormone</subject><subject>Dependovirus - metabolism</subject><subject>Energy Metabolism</subject><subject>Feeding Behavior</subject><subject>Food intake</subject><subject>GABAergic Neurons - metabolism</subject><subject>Gene Deletion</subject><subject>Gene expression</subject><subject>Glutamates - metabolism</subject><subject>Hormones</subject><subject>humans</subject><subject>Hyperphagia</subject><subject>Injections</subject><subject>Integrases - metabolism</subject><subject>Mass</subject><subject>Melanocortins</subject><subject>Mice</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neuropeptides - metabolism</subject><subject>Obesity</subject><subject>oxytocin</subject><subject>Parabrachial Nucleus - metabolism</subject><subject>paraventricular hypothalamic nucleus</subject><subject>Paraventricular Hypothalamic Nucleus - metabolism</subject><subject>Receptor, Melanocortin, Type 4 - metabolism</subject><subject>Receptors</subject><subject>Repressor Proteins - metabolism</subject><subject>Reproducibility of Results</subject><subject>rodents</subject><subject>Satiety</subject><subject>Stereotaxic Techniques</subject><subject>Synapses - metabolism</subject><subject>vasopressin</subject><subject>Vesicular Glutamate Transport Protein 2 - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkkuP1DAQhCMEYpeFMyfAEhcu2XXbjpNckNCIl7QICdiz1eN0Mhll7GA7K-aH8H9JmGF4nDhZcn1dcpcryx4DvwReyqvRYbwExctKSQC4k50DryHXquZ3s3PORZlXSqiz7EGMW855XVT8fnYmCihKUOo8-_5hpT7l9G0MFGPvOtYNU8IdJgpdb5mjKXgXWe9Y2hAbMeAtuRR6Ow0Y2GY_-rTBAXdTZIG6-TIRa4maxQpdwzAQi3uHY-otDsOeWe8c2UQNS_7kuQ5oNz0OzE12oCk-zO61OER6dDwvsps3r7-s3uXXH9--X726zq0WKuWIEgEaxRXpVmhRSdBK8Lq1raxa4lpgoeqZ4ZqqUq2pgXUrSwSr15UAJS-ylwffcVrvqLHLajiYMfQ7DHvjsTd_K67fmM7fmjlTXReLwYujQfBfJ4rJ7PpoaRjQkZ-igYrLOfRS_Qeqa1WXotAL-vwfdOun4OYkDMz6_I_iJ3V1oGzwMQZqT-8GbpZ2mKUd5nc75omnf6574n_VYQbYEVgmT3YARmoDEmo5I08OyDYmH06MklxJyRf92UFv0RvsQh_NzWfBQXM-B16XUv4AmEvWdA</recordid><startdate>20140909</startdate><enddate>20140909</enddate><creator>Shah, Bhavik P.</creator><creator>Vong, Linh</creator><creator>Olson, David P.</creator><creator>Koda, Shuichi</creator><creator>Krashes, Michael J.</creator><creator>Ye, Chianping</creator><creator>Yang, Zongfang</creator><creator>Fuller, Patrick M.</creator><creator>Elmquist, Joel K.</creator><creator>Lowell, Bradford B.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20140909</creationdate><title>MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus</title><author>Shah, Bhavik P. ; 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Unfortunately, the underlying neural mechanisms by which MC4Rs regulate food intake are poorly understood. Unraveling these mechanisms may open up avenues for treating obesity. In the present study we have established that MC4Rs on neurons in the paraventricular nucleus of the hypothalamus are both necessary and sufficient for MC4R control of feeding and that these neurons are glutamatergic and not GABAergic and do not express the neuropeptides oxytocin, corticotropin-releasing hormone, prodynorphin, or vasopressin. In addition, we identify downstream projections from these glutamatergic neurons to the lateral parabrachial nucleus, which could mediate the appetite suppressing effects.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>25157144</pmid><doi>10.1073/pnas.1407843111</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals appetite Basic Helix-Loop-Helix Transcription Factors - metabolism Biological Sciences Body Weight Brain corticotropin-releasing hormone Dependovirus - metabolism Energy Metabolism Feeding Behavior Food intake GABAergic Neurons - metabolism Gene Deletion Gene expression Glutamates - metabolism Hormones humans Hyperphagia Injections Integrases - metabolism Mass Melanocortins Mice Neurons Neurons - metabolism Neuropeptides - metabolism Obesity oxytocin Parabrachial Nucleus - metabolism paraventricular hypothalamic nucleus Paraventricular Hypothalamic Nucleus - metabolism Receptor, Melanocortin, Type 4 - metabolism Receptors Repressor Proteins - metabolism Reproducibility of Results rodents Satiety Stereotaxic Techniques Synapses - metabolism vasopressin Vesicular Glutamate Transport Protein 2 - metabolism |
| title | MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus |
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