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PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice.

AbstractOBJECTIVE:
Peptide YY (PYY3-36) and pancreatic polypeptide (PP) potently inhibit food intake in rodents and humans, however, it is unclear whether they have any synergistic/additive interaction in decreasing food intake.
DESIGN AND METHODS:
Fasted WT, Y2(-) (/) (-) , Y4(-) (/) (-) , or Y2Y4(-) (/) (-) mice were i.p. administrated with saline, PYY3-36, and/or PP.
RESULTS:
Combined injection of PYY3-36 and PP reduces food intake in an additive manner was demonstrated in this study. This effect is mediated via Y2 and Y4 receptors, respectively. It was demonstrated that PYY3-36 and PP activate distinct neuronal pathways in the hypothalamus, as demonstrated by immunostaining for c-fos, which shows distinct patterns in response to either hormone. After PYY3-36 injection, neurons in the dorsal aspect of the arcuate nucleus (Arc), paraventricular nucleus, and dorso-medial nucleus of the hypothalamus (DMH) are activated with minimal responses seen in the ventro-medial nucleus of the hypothalamus (VMH) and lateral hypothalamic area (LHA) of WT mice. These effects are absent in Y2(-) (/) (-) mice. PP activates preferably the lateral aspect of the Arc, the DMH, VMH, and LHA in a Y4 receptor-dependent manner. Importantly, the expression pattern of c-fos immunoreactive neurons induced by combined treatment appears to be the sum of the effects of single treatments rather than a result of synergistic interaction.
CONCLUSIONS:
These findings demonstrate that PYY3-36 and PP activate distinct pathways in the hypothalamus to reduce food intake in an additive manner.
AuthorsYan-Chuan Shi, Zhou Lin, Jackie Lau, Hui Zhang, Miyuki Yagi, Isabella Kanzler, Amanda Sainsbury, Herbert Herzog, Shu Lin
JournalObesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 21 Issue 12 Pg. E669-78 (Dec 2013) ISSN: 1930-739X [Electronic] United States
PMID23804428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 The Obesity Society.
Chemical References
  • Peptide Fragments
  • Proto-Oncogene Proteins c-fos
  • Receptors, Neuropeptide Y
  • neuropeptide Y2 receptor
  • neuropeptide Y4 receptor
  • Peptide YY
  • peptide YY (3-36)
  • Pancreatic Polypeptide
Topics
  • Animals
  • Arcuate Nucleus of Hypothalamus (drug effects, metabolism)
  • Body Weight (drug effects)
  • Eating (drug effects)
  • Fasting
  • Immunohistochemistry
  • MAP Kinase Signaling System (genetics)
  • Male
  • Mice
  • Mice, Knockout
  • Neurons (drug effects, metabolism)
  • Pancreatic Polypeptide (administration & dosage)
  • Paraventricular Hypothalamic Nucleus (drug effects, metabolism)
  • Peptide Fragments (administration & dosage)
  • Peptide YY (administration & dosage)
  • Proto-Oncogene Proteins c-fos (genetics, metabolism)
  • Receptors, Neuropeptide Y (genetics, metabolism)

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