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PYY3‐36 and pancreatic polypeptide reduce food intake in an additive manner via distinct hypothalamic dependent pathways in mice
Author(s) -
Shi YanChuan,
Lin Zhou,
Lau Jackie,
Zhang Hui,
Yagi Miyuki,
Kanzler Isabella,
Sainsbury Amanda,
Herzog Herbert,
Lin Shu
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20534
Subject(s) - hypothalamus , endocrinology , medicine , nucleus , receptor , lateral hypothalamus , arcuate nucleus , arc (geometry) , food intake , biology , chemistry , microbiology and biotechnology , geometry , mathematics
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.