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Publication
Excitatory transmission onto AgRP neurons is regulated by cJun NH2-terminal
kinase 3 in response to metabolic stress.
Authors Vernia S, Morel C, Madara JC, Cavanagh-Kyros J, Barrett T, Chase K, Kennedy NJ,
Jung DY, Kim JK, Aronin N, Flavell RA, Lowell BB, Davis RJ
Submitted By Submitted Externally on 7/20/2016
Status Published
Journal eLife
Year 2016
Date Published
Volume : Pages 5 : e10031
PubMed Reference 26910012
Abstract 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.




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