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Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals
PLoS Genetics (2012)
  • Seung-Hyun Hong, Korea Research Institute of Bioscience and Biotechnology
  • Kyu-Sun Lee, Korea Research Institute of Bioscience and Biotechnology
  • Su-Jin Kwak, Korea Research Institute of Bioscience and Biotechnology
  • Ae-Kyeong Kim, Korea Research Institute of Bioscience and Biotechnology
  • Hua Bai, Brown University
  • Min-Su Jung, Inje University
  • O-Yu Kwon, Chungnam National University
  • Woo-Joo Song, Inje University
  • Marc Tatar, Brown University
  • Kweon Yu, Korea Research Institute of Bioscience and Biotechnology
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.
Publication Date
August, 2012
DOI
10.1371/journal.pgen.1002857
Publisher Statement
 Copyright 2012 Hong et al.
Citation Information
Seung-Hyun Hong, Kyu-Sun Lee, Su-Jin Kwak, Ae-Kyeong Kim, et al.. "Minibrain/Dyrk1a Regulates Food Intake through the Sir2-FOXO-sNPF/NPY Pathway in Drosophila and Mammals" PLoS Genetics Vol. 8 Iss. 8 (2012) p. e1002857
Available at: http://works.bepress.com/hua-bai/8/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY International License.