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dc.contributor.authorVernia, Santiago
dc.contributor.authorMorel, Caroline
dc.contributor.authorMadara, Joseph C.
dc.contributor.authorCavanagh-Kyros, Julie
dc.contributor.authorBarrett, Tamera
dc.contributor.authorChase, Kathryn O.
dc.contributor.authorKennedy, Norman J.
dc.contributor.authorJung, Dae Young
dc.contributor.authorKim, Jason K.
dc.contributor.authorAronin, Neil
dc.contributor.authorFlavell, Richard A.
dc.contributor.authorLowell, Bradford B.
dc.contributor.authorDavis, Roger J.
dc.date2022-08-11T08:08:16.000
dc.date.accessioned2022-08-23T15:49:00Z
dc.date.available2022-08-23T15:49:00Z
dc.date.issued2016-02-24
dc.date.submitted2016-04-22
dc.identifier.citationElife. 2016 Feb 24;5. pii: e10031. doi: 10.7554/eLife.10031. <a href="http://dx.doi.org/10.7554/eLife.10031">Link to article on publisher's site</a>
dc.identifier.issn2050-084X (Linking)
dc.identifier.doi10.7554/eLife.10031
dc.identifier.pmid26910012
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28329
dc.description.abstractThe cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These effects of JNK3 deficiency were associated with enhanced excitatory signaling by AgRP neurons in HFD-fed mice. JNK3 therefore provides a mechanism that contributes to homeostatic regulation of energy balance in response to metabolic stress.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26910012&dopt=Abstract">Link to Article in PubMed</a>
dc.rights<p>© 2016, Vernia et al. This article is distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">Creative Commons Attribution License</a>, which permits unrestricted use and redistribution provided that the original author and source are credited.</p>
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectJNK
dc.subjectcell biology
dc.subjectleptin
dc.subjectmouse
dc.subjectneuroscience
dc.subjectsatiety
dc.subjectsignal transduction
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular and Cellular Neuroscience
dc.subjectMolecular Biology
dc.titleExcitatory transmission onto AgRP neurons is regulated by cJun NH2-terminal kinase 3 in response to metabolic stress
dc.typeJournal Article
dc.source.journaltitleeLife
dc.source.volume5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1055&amp;context=davis&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/davis/56
dc.identifier.contextkey8511806
refterms.dateFOA2022-08-23T15:49:00Z
html.description.abstract<p>The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These effects of JNK3 deficiency were associated with enhanced excitatory signaling by AgRP neurons in HFD-fed mice. JNK3 therefore provides a mechanism that contributes to homeostatic regulation of energy balance in response to metabolic stress.</p>
dc.identifier.submissionpathdavis/56
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes
dc.contributor.departmentProgram in Molecular Medicine


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<p>© 2016, Vernia et al. This article is distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">Creative Commons Attribution License</a>, which permits unrestricted use and redistribution provided that the original author and source are credited.</p>
Except where otherwise noted, this item's license is described as <p>© 2016, Vernia et al. This article is distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">Creative Commons Attribution License</a>, which permits unrestricted use and redistribution provided that the original author and source are credited.</p>