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

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  • Ken-ichiro Nakajima

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases
    Present address: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan)

  • Zhenzhong Cui

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Chia Li

    (Diabetes Endocrine and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jaroslawna Meister

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Yinghong Cui

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Ou Fu

    (Graduate School of Agricultural and Life Sciences, The University of Tokyo)

  • Adam S. Smith

    (Section on Neural Gene Expression, National Institute of Mental Health)

  • Shalini Jain

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Bradford B. Lowell

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Michael J. Krashes

    (Diabetes Endocrine and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases)

  • Jürgen Wess

    (Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases)

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.

Suggested Citation

  • Ken-ichiro Nakajima & Zhenzhong Cui & Chia Li & Jaroslawna Meister & Yinghong Cui & Ou Fu & Adam S. Smith & Shalini Jain & Bradford B. Lowell & Michael J. Krashes & Jürgen Wess, 2016. "Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake," Nature Communications, Nature, vol. 7(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10268
    DOI: 10.1038/ncomms10268
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    Cited by:

    1. Tasuku Kawano & Jinyan Zhou & Shehata Anwar & Haneen Salah & Andrea H. Dayal & Yuzuki Ishikawa & Katelyn Boetel & Tomoko Takahashi & Kamal Sharma & Makoto Inoue, 2023. "T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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