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

Autor: Yan-Chuan Shi, Herbert Herzog, Miyuki Yagi, Shu Lin, Zhou Lin, Amanda Sainsbury, Jackie Lau, Hui Zhang, Isabella Kanzler
Rok vydání: 2013
Předmět:
Zdroj: Obesity. 21:E669-E678
ISSN: 1930-7381
DOI: 10.1002/oby.20534
Popis: 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.
Databáze: OpenAIRE
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