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

Abstract

OBJECTIVE:

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.

• Authors: Yan-Chuan Shi, Zhou Lin, Jackie Lau, Hui Zhang, Miyuki Yagi, Isabella Kanzler, Amanda Sainsbury, Herbert Herzog, Shu Lin
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 21 Issue 12 Pg. E669-78 (Dec 2013) ISSN: 1930-739X [Electronic] United States
• PMID: 23804428 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 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)