Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake
Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-l...
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| creator | Jeong, Jae Hoon Lee, Dong Kun Liu, Shun-Mei Chua, Jr, Streamson C Schwartz, Gary J Jo, Young-Hwan |
| description | Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake. |
| doi_str_mv | 10.1371/journal.pbio.2004399 |
| format | Article |
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Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.</description><identifier>ISSN: 1545-7885</identifier><identifier>ISSN: 1544-9173</identifier><identifier>EISSN: 1545-7885</identifier><identifier>DOI: 10.1371/journal.pbio.2004399</identifier><identifier>PMID: 29689050</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Activation ; Animals ; Appetite ; Arcuate nucleus ; Arcuate Nucleus of Hypothalamus - cytology ; Arcuate Nucleus of Hypothalamus - drug effects ; Arcuate Nucleus of Hypothalamus - metabolism ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Biology and Life Sciences ; Body temperature ; Capsaicin ; Capsaicin - pharmacology ; Capsaicin receptors ; Channelrhodopsins - genetics ; Channelrhodopsins - metabolism ; CRISPR ; Data collection ; Depolarization ; Eating - drug effects ; Eating - genetics ; Electrophysiology ; Endocrinology ; Enhancer Elements, Genetic ; Enhancers ; Female ; Fitness equipment ; Fluorescence ; Food ; Food intake ; Gene expression ; Gene Expression Regulation ; Gene Knock-In Techniques ; Gene Knockout Techniques ; Genes, Reporter ; Hypothalamus ; Immunohistochemistry ; Ion channels ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Male ; Medicine ; Medicine and Health Sciences ; Melanocortin ; Mice ; Mice, Transgenic ; Neural circuitry ; Neurons ; Neurons - cytology ; Neurons - drug effects ; Neurons - metabolism ; Optogenetics ; Physical Conditioning, Animal ; Physiological aspects ; Physiology ; Polymerase chain reaction ; Pro-Opiomelanocortin - genetics ; Pro-Opiomelanocortin - metabolism ; Proopiomelanocortin ; Proteins ; Receptors ; Receptors, Melanocortin - genetics ; Receptors, Melanocortin - metabolism ; Research and Analysis Methods ; Reverse transcription ; Rodents ; Running ; Signal Transduction ; Single-Cell Analysis ; Temperature ; Temperature effects ; Transient receptor potential proteins ; TRPV Cation Channels - agonists ; TRPV Cation Channels - deficiency ; TRPV Cation Channels - genetics ; Viruses ; Weight control ; Yellow fluorescent protein</subject><ispartof>PLoS biology, 2018-04, Vol.16 (4), p.e2004399-e2004399</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Jeong JH, Lee DK, Liu S-M, Chua SC Jr, Schwartz GJ, Jo Y-H (2018) Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake. PLoS Biol 16(4): e2004399. https://doi.org/10.1371/journal.pbio.2004399</rights><rights>2018 Jeong et al 2018 Jeong et al</rights><rights>2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Jeong JH, Lee DK, Liu S-M, Chua SC Jr, Schwartz GJ, Jo Y-H (2018) Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake. PLoS Biol 16(4): e2004399. https://doi.org/10.1371/journal.pbio.2004399</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c838t-cb2d89a2e66a3842d9cd354e9cbfb3794ae36fad2ae863f004316b7084c38dff3</citedby><cites>FETCH-LOGICAL-c838t-cb2d89a2e66a3842d9cd354e9cbfb3794ae36fad2ae863f004316b7084c38dff3</cites><orcidid>0000-0001-6939-8000</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915833/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915833/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29689050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeong, Jae Hoon</creatorcontrib><creatorcontrib>Lee, Dong Kun</creatorcontrib><creatorcontrib>Liu, Shun-Mei</creatorcontrib><creatorcontrib>Chua, Jr, Streamson C</creatorcontrib><creatorcontrib>Schwartz, Gary J</creatorcontrib><creatorcontrib>Jo, Young-Hwan</creatorcontrib><title>Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake</title><title>PLoS biology</title><addtitle>PLoS Biol</addtitle><description>Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.</description><subject>Activation</subject><subject>Animals</subject><subject>Appetite</subject><subject>Arcuate nucleus</subject><subject>Arcuate Nucleus of Hypothalamus - cytology</subject><subject>Arcuate Nucleus of Hypothalamus - drug effects</subject><subject>Arcuate Nucleus of Hypothalamus - metabolism</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Biology and Life Sciences</subject><subject>Body temperature</subject><subject>Capsaicin</subject><subject>Capsaicin - pharmacology</subject><subject>Capsaicin receptors</subject><subject>Channelrhodopsins - genetics</subject><subject>Channelrhodopsins - metabolism</subject><subject>CRISPR</subject><subject>Data collection</subject><subject>Depolarization</subject><subject>Eating - drug effects</subject><subject>Eating - genetics</subject><subject>Electrophysiology</subject><subject>Endocrinology</subject><subject>Enhancer Elements, Genetic</subject><subject>Enhancers</subject><subject>Female</subject><subject>Fitness equipment</subject><subject>Fluorescence</subject><subject>Food</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gene Knock-In Techniques</subject><subject>Gene Knockout Techniques</subject><subject>Genes, Reporter</subject><subject>Hypothalamus</subject><subject>Immunohistochemistry</subject><subject>Ion channels</subject><subject>Luminescent Proteins - genetics</subject><subject>Luminescent Proteins - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Melanocortin</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Neural circuitry</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Neurons - drug effects</subject><subject>Neurons - metabolism</subject><subject>Optogenetics</subject><subject>Physical Conditioning, Animal</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Polymerase chain reaction</subject><subject>Pro-Opiomelanocortin - genetics</subject><subject>Pro-Opiomelanocortin - metabolism</subject><subject>Proopiomelanocortin</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, Melanocortin - genetics</subject><subject>Receptors, Melanocortin - metabolism</subject><subject>Research and Analysis Methods</subject><subject>Reverse transcription</subject><subject>Rodents</subject><subject>Running</subject><subject>Signal Transduction</subject><subject>Single-Cell Analysis</subject><subject>Temperature</subject><subject>Temperature effects</subject><subject>Transient receptor potential proteins</subject><subject>TRPV Cation Channels - agonists</subject><subject>TRPV Cation Channels - deficiency</subject><subject>TRPV Cation Channels - genetics</subject><subject>Viruses</subject><subject>Weight control</subject><subject>Yellow fluorescent protein</subject><issn>1545-7885</issn><issn>1544-9173</issn><issn>1545-7885</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqVk99v0zAQxyMEYmPwHyCIxAs8pNhxnNgvSFXFj0qDTmXs1Tj2ubhL42I7E_z3uGs2rWgPID_Yuvvc93xnX5Y9x2iCSYPfrt3ge9lNtq11kxKhinD-IDvGtKJFwxh9eOd8lD0JYY1QWfKSPc6OSl4zjig6zr5PVbRXMlrX587kETZb8DIOHooAfbDJCfn58uwCF529hNyDgm10PuS2z6fLWX62-DzLexi860Py6kFByI1zOgFRXsLT7JGRXYBn436Sffvw_nz2qThdfJzPpqeFYoTFQrWlZlyWUNeSsKrUXGlCK-CqNS1peCWB1EbqUgKridmVi-u2QaxShGljyEn2cq-77VwQY3OCKBHhTU1TjkTM94R2ci223m6k_y2ctOLa4PxKSB-t6kAggpGkqmp0q6vGECkZarSuGWBOK02T1rsx29BuQCvoo5fdgeihp7c_xMpdCcpxugxJAq9HAe9-DhCi2NigoOtkD264vjfimLAaJ_TVX-j91Y3USqYCbG9cyqt2omJKSc0QpwglanIPlZaGjVWuB2OT_SDgzUFAYiL8iis5hCDmX5f_wX75d3ZxcchWe1Z5F4IHc9tnjMRuFm4aInazIMZZSGEv7r7RbdDN5yd_AKbeA7s</recordid><startdate>20180424</startdate><enddate>20180424</enddate><creator>Jeong, Jae Hoon</creator><creator>Lee, Dong Kun</creator><creator>Liu, Shun-Mei</creator><creator>Chua, Jr, Streamson C</creator><creator>Schwartz, Gary J</creator><creator>Jo, Young-Hwan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PATMY</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZG</scope><orcidid>https://orcid.org/0000-0001-6939-8000</orcidid></search><sort><creationdate>20180424</creationdate><title>Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake</title><author>Jeong, Jae Hoon ; Lee, Dong Kun ; Liu, Shun-Mei ; Chua, Jr, Streamson C ; Schwartz, Gary J ; Jo, Young-Hwan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c838t-cb2d89a2e66a3842d9cd354e9cbfb3794ae36fad2ae863f004316b7084c38dff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Activation</topic><topic>Animals</topic><topic>Appetite</topic><topic>Arcuate nucleus</topic><topic>Arcuate Nucleus of Hypothalamus - cytology</topic><topic>Arcuate Nucleus of Hypothalamus - drug effects</topic><topic>Arcuate Nucleus of Hypothalamus - metabolism</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - metabolism</topic><topic>Biology and Life Sciences</topic><topic>Body temperature</topic><topic>Capsaicin</topic><topic>Capsaicin - pharmacology</topic><topic>Capsaicin receptors</topic><topic>Channelrhodopsins - genetics</topic><topic>Channelrhodopsins - metabolism</topic><topic>CRISPR</topic><topic>Data collection</topic><topic>Depolarization</topic><topic>Eating - drug effects</topic><topic>Eating - genetics</topic><topic>Electrophysiology</topic><topic>Endocrinology</topic><topic>Enhancer Elements, Genetic</topic><topic>Enhancers</topic><topic>Female</topic><topic>Fitness equipment</topic><topic>Fluorescence</topic><topic>Food</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene Knock-In Techniques</topic><topic>Gene Knockout Techniques</topic><topic>Genes, Reporter</topic><topic>Hypothalamus</topic><topic>Immunohistochemistry</topic><topic>Ion channels</topic><topic>Luminescent Proteins - genetics</topic><topic>Luminescent Proteins - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Melanocortin</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Neural circuitry</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Neurons - drug effects</topic><topic>Neurons - metabolism</topic><topic>Optogenetics</topic><topic>Physical Conditioning, Animal</topic><topic>Physiological aspects</topic><topic>Physiology</topic><topic>Polymerase chain reaction</topic><topic>Pro-Opiomelanocortin - genetics</topic><topic>Pro-Opiomelanocortin - metabolism</topic><topic>Proopiomelanocortin</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Receptors, Melanocortin - genetics</topic><topic>Receptors, Melanocortin - metabolism</topic><topic>Research and Analysis Methods</topic><topic>Reverse transcription</topic><topic>Rodents</topic><topic>Running</topic><topic>Signal Transduction</topic><topic>Single-Cell Analysis</topic><topic>Temperature</topic><topic>Temperature effects</topic><topic>Transient receptor potential proteins</topic><topic>TRPV Cation Channels - agonists</topic><topic>TRPV Cation Channels - deficiency</topic><topic>TRPV Cation Channels - genetics</topic><topic>Viruses</topic><topic>Weight control</topic><topic>Yellow fluorescent protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jeong, Jae Hoon</creatorcontrib><creatorcontrib>Lee, Dong Kun</creatorcontrib><creatorcontrib>Liu, Shun-Mei</creatorcontrib><creatorcontrib>Chua, Jr, Streamson C</creatorcontrib><creatorcontrib>Schwartz, Gary J</creatorcontrib><creatorcontrib>Jo, Young-Hwan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Canada</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Biology</collection><jtitle>PLoS biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jeong, Jae Hoon</au><au>Lee, Dong Kun</au><au>Liu, Shun-Mei</au><au>Chua, Jr, Streamson C</au><au>Schwartz, Gary J</au><au>Jo, Young-Hwan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake</atitle><jtitle>PLoS biology</jtitle><addtitle>PLoS Biol</addtitle><date>2018-04-24</date><risdate>2018</risdate><volume>16</volume><issue>4</issue><spage>e2004399</spage><epage>e2004399</epage><pages>e2004399-e2004399</pages><issn>1545-7885</issn><issn>1544-9173</issn><eissn>1545-7885</eissn><abstract>Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29689050</pmid><doi>10.1371/journal.pbio.2004399</doi><orcidid>https://orcid.org/0000-0001-6939-8000</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1545-7885 |
| ispartof | PLoS biology, 2018-04, Vol.16 (4), p.e2004399-e2004399 |
| issn | 1545-7885 1544-9173 1545-7885 |
| language | eng |
| recordid | cdi_plos_journals_2039765838 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Activation Animals Appetite Arcuate nucleus Arcuate Nucleus of Hypothalamus - cytology Arcuate Nucleus of Hypothalamus - drug effects Arcuate Nucleus of Hypothalamus - metabolism Bacterial Proteins - genetics Bacterial Proteins - metabolism Biology and Life Sciences Body temperature Capsaicin Capsaicin - pharmacology Capsaicin receptors Channelrhodopsins - genetics Channelrhodopsins - metabolism CRISPR Data collection Depolarization Eating - drug effects Eating - genetics Electrophysiology Endocrinology Enhancer Elements, Genetic Enhancers Female Fitness equipment Fluorescence Food Food intake Gene expression Gene Expression Regulation Gene Knock-In Techniques Gene Knockout Techniques Genes, Reporter Hypothalamus Immunohistochemistry Ion channels Luminescent Proteins - genetics Luminescent Proteins - metabolism Male Medicine Medicine and Health Sciences Melanocortin Mice Mice, Transgenic Neural circuitry Neurons Neurons - cytology Neurons - drug effects Neurons - metabolism Optogenetics Physical Conditioning, Animal Physiological aspects Physiology Polymerase chain reaction Pro-Opiomelanocortin - genetics Pro-Opiomelanocortin - metabolism Proopiomelanocortin Proteins Receptors Receptors, Melanocortin - genetics Receptors, Melanocortin - metabolism Research and Analysis Methods Reverse transcription Rodents Running Signal Transduction Single-Cell Analysis Temperature Temperature effects Transient receptor potential proteins TRPV Cation Channels - agonists TRPV Cation Channels - deficiency TRPV Cation Channels - genetics Viruses Weight control Yellow fluorescent protein |
| title | Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake |
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