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Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals.
- Source :
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PLoS genetics [PLoS Genet] 2012; Vol. 8 (8), pp. e1002857. Date of Electronic Publication: 2012 Aug 02. - Publication Year :
- 2012
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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, [corrected] 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, and [corrected] 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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Acetylation
Animals
Drosophila Proteins genetics
Drosophila Proteins metabolism
Drosophila melanogaster physiology
Forkhead Box Protein O1
Forkhead Transcription Factors genetics
Forkhead Transcription Factors metabolism
Humans
Hypothalamus physiology
Mammals physiology
Mice
Neuropeptide Y genetics
Neuropeptide Y metabolism
Neuropeptides genetics
Neuropeptides metabolism
Protein Serine-Threonine Kinases genetics
Protein Serine-Threonine Kinases metabolism
Protein-Tyrosine Kinases genetics
Protein-Tyrosine Kinases metabolism
Sirtuin 1 genetics
Sirtuin 1 metabolism
Dyrk Kinases
Appetite Regulation genetics
Eating physiology
Feeding Behavior physiology
Gene Expression Regulation
Signal Transduction genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 22876196
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002857