Herbert Herzog and Shu Lin contributed equally to this work.
PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice
Article first published online: 5 SEP 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 12, pages E669–E678, December 2013
How to Cite
Shi, Y.-C., Lin, Z., Lau, J., Zhang, H., Yagi, M., Kanzler, I., Sainsbury, A., Herzog, H. and Lin, S. (2013), PYY3-36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice. Obesity, 21: E669–E678. doi: 10.1002/oby.20534
Funding agencies: This study was supported by the National Health and Medical Research Council (NHMRC) of Australia with grant #427661 and fellowships to SL, AS, and HH.
Author contributions: Conceived and designed the experiments: SL HH. Carried out the experiments: SL YCS ZL JL IK MY. Analyzed the data: SL YCS. Wrote the manuscript: YCS HH AS SL. All authors had final approval of the submitted and published versions.
Disclosure: The authors declared no conflict of interest.
- Issue published online: 3 DEC 2013
- Article first published online: 5 SEP 2013
- Accepted manuscript online: 26 JUN 2013 12:49PM EST
- Manuscript Accepted: 18 MAY 2013
- Manuscript Received: 14 MAY 2013
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.
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.
These findings demonstrate that PYY3-36 and PP activate distinct pathways in the hypothalamus to reduce food intake in an additive manner.