UMMS Affiliation

Program in Molecular Medicine; Department of Medicine, Division of Endocrinology, Metabolism and Diabetes; UMass Metabolic Network

Date

2-24-2016

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular and Cellular Neuroscience | Molecular Biology

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.

Rights and Permissions

Citation: Elife. 2016 Feb 24;5. pii: e10031. doi: 10.7554/eLife.10031. Link to article on publisher's site

Comments

© 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.

Related Resources

Link to Article in PubMed

Keywords

JNK, cell biology, leptin, mouse, neuroscience, satiety, signal transduction

PubMed ID

26910012

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

 
 

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