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

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

Abstract

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.

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / metabolism
  • Anxiety / physiopathology
  • Arcuate Nucleus of Hypothalamus / metabolism*
  • Arcuate Nucleus of Hypothalamus / physiopathology
  • Eating / physiology
  • Feeding Behavior*
  • Gene Expression
  • Ghrelin / genetics
  • Ghrelin / metabolism
  • Glucose / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Leptin / genetics
  • Leptin / metabolism
  • Locomotion
  • Male
  • Mice
  • Mice, Knockout
  • Neurons / metabolism*
  • Neurons / pathology
  • Peptides / deficiency
  • Peptides / genetics*
  • Signal Transduction
  • Wakefulness / physiology*

Substances

  • Ghrelin
  • Intercellular Signaling Peptides and Proteins
  • Leptin
  • Peptides
  • QRFP peptide
  • Glucose

Grants and funding

This research was funded by the Cabinet Office, Government of Japan through its “Funding Program for Next Generation World-Leading Researchers.” This work was also supported by a Grant-in-Aid for Scientific Research on Priority Areas – Integrative Brain Research (IBR-shien) – and a Grant-in-Aid for Scientific Research on Innovative Areas (16H06401) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.