Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

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Nakajima, Ken-ichiro
Cui, Zhenzhong
Li, Chia
Meister, Jaroslawna
Cui, Yinghong
Fu, Ou
Smith, Adam S.
Jain, Shalini
Krashes, Michael J.
Wess, Jürgen
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ncomms10268Metadata
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Nakajima, K., Z. Cui, C. Li, J. Meister, Y. Cui, O. Fu, A. S. Smith, et al. 2016. “Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.” Nature Communications 7 (1): 10268. doi:10.1038/ncomms10268. http://dx.doi.org/10.1038/ncomms10268.Abstract
Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729878/pdf/Terms of Use
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