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© 2012 Hong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hong S-H, Lee K-S, Kwak S-J, Kim A-K, Bai H, et al. (2012) Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals. PLoS Genet 8(8): e1002857. doi:10.1371/journal.pgen.1002857

Abstract

Feeding behavior is one of the most essential activities in animals, which is tightly regulated by neuroendocrine factors. Drosophila melanogaster short neuropeptide F (sNPF) and the mammalian functional homolog neuropeptide Y (NPY) regulate food intake. Understanding the molecular mechanism of sNPF and NPY signaling is critical to elucidate feeding regulation. Here, we found that minibrain (mnb) and the mammalian ortholog Dyrk1a target genes of sNPF and NPY signaling and regulate food intake in Drosophila melanogaster and mice. In Drosophila melanogaster neuronal cells and mouse hypothalamic cells, sNPF and NPY modulated the mnb and Dyrk1a expression through the PKA-CREB pathway. Increased Dyrk1a activated Sirt1 to regulate the deacetylation of FOXO, which potentiated FOXO-induced sNPF/NPY expression and in turn promoted food intake. Conversely, AKT-mediated insulin signaling suppressed FOXO-mediated sNPF/NPY expression, which resulted in decreasing food intake. Furthermore, human Dyrk1a transgenic mice exhibited decreased FOXO acetylation and increased NPY expression in the hypothalamus, as well as increased food intake. Our findings demonstrate that Mnb/Dyrk1a regulates food intake through the evolutionary conserved Sir2-FOXO-sNPF/NPY pathway in Drosophila melanogaster and mammals.

Details

Title
Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals
Author
Hong, Seung-Hyun; Lee, Kyu-Sun; Kwak, Su-Jin; Kim, Ae-Kyeong; Bai, Hua; Jung, Min-Su; Kwon, O-Yu; Song, Woo-Joo; Tatar, Marc; Yu, Kweon
Section
Research Article
Publication year
2012
Publication date
Aug 2012
Publisher
Public Library of Science
ISSN
15537390
e-ISSN
15537404
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1313539387
Copyright
© 2012 Hong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Hong S-H, Lee K-S, Kwak S-J, Kim A-K, Bai H, et al. (2012) Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals. PLoS Genet 8(8): e1002857. doi:10.1371/journal.pgen.1002857