Excitatory transmission onto AgRP neurons is regulated by cJun NH2-terminal kinase 3 in response to metabolic stress
Authors
Vernia, SantiagoMorel, Caroline
Madara, Joseph C.
Cavanagh-Kyros, Julie
Barrett, Tamera
Chase, Kathryn O.
Kennedy, Norman J.
Jung, Dae Young
Kim, Jason K.
Aronin, Neil
Flavell, Richard A.
Lowell, Bradford B.
Davis, Roger J.
UMass Chan Affiliations
UMass Metabolic NetworkDepartment of Medicine, Division of Endocrinology, Metabolism and Diabetes
Program in Molecular Medicine
Document Type
Journal ArticlePublication Date
2016-02-24Keywords
JNKcell biology
leptin
mouse
neuroscience
satiety
signal transduction
Biochemistry
Cell Biology
Cellular and Molecular Physiology
Molecular and Cellular Neuroscience
Molecular Biology
Metadata
Show full item recordAbstract
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.Source
Elife. 2016 Feb 24;5. pii: e10031. doi: 10.7554/eLife.10031. Link to article on publisher's siteDOI
10.7554/eLife.10031Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28329PubMed ID
26910012Related Resources
Link to Article in PubMedRights
© 2016, Vernia et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.7554/eLife.10031
Scopus Count
Collections
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>