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PLoS One. 2016 Nov 11;11(11):e0164716. doi: 10.1371/journal.pone.0164716. eCollection 2016.

QRFP-Deficient Mice Are Hypophagic, Lean, Hypoactive and Exhibit Increased Anxiety-Like Behavior.

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Department of Molecular Neuroscience and Integrative Physiology, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan.
Department of Anatomy, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido 060-8638, Japan.
Section of Behavior Patterns, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, 38 Nishigonaka Myodaiji, Okazaki, Aichi, 444-8585, Japan.
Division of Animal Resources and Development, Life Science Research Center, University of Toyama, Toyama, 930-8555, Japan.
Division of Metabolic Medicine, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo 153-8904, Japan.
ERATO Yanagisawa Orphan Receptor Project, Japan Science and Technology Agency, Tokyo 135-0064, Japan.
Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, 470-1192, Japan.
Faculty of Medicine/International Institute for Integrative Sleep Medicine (IIIS), University of Tsukuba, Tsukuba 305-8575, Japan.


How the hypothalamus transmits hunger information to other brain regions to govern whole brain function to orchestrate feeding behavior has remained largely unknown. Our present study suggests the importance of a recently found lateral hypothalamic neuropeptide, QRFP, in this signaling. Qrfp-/- mice were hypophagic and lean, and exhibited increased anxiety-like behavior, and were hypoactive in novel circumstances as compared with wild type littermates. They also showed decreased wakefulness time in the early hours of the dark period. Histological studies suggested that QRFP neurons receive rich innervations from neurons in the arcuate nucleus which is a primary region for sensing the body's metabolic state by detecting levels of leptin, ghrelin and glucose. These observations suggest that QRFP is an important mediator that acts as a downstream mediator of the arcuate nucleus and regulates feeding behavior, mood, wakefulness and activity.

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