A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster
Abstract Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress exce...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55050-y |
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| author | Yuto Yoshinari Takashi Nishimura Taishi Yoshii Shu Kondo Hiromu Tanimoto Tomoe Kobayashi Makoto Matsuyama Ryusuke Niwa |
| author_facet | Yuto Yoshinari Takashi Nishimura Taishi Yoshii Shu Kondo Hiromu Tanimoto Tomoe Kobayashi Makoto Matsuyama Ryusuke Niwa |
| author_sort | Yuto Yoshinari |
| collection | DOAJ |
| description | Abstract Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload. |
| format | Article |
| id | doaj-art-72179c88f3844fa5b28f8ec338da0124 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-72179c88f3844fa5b28f8ec338da01242025-01-05T12:36:49ZengNature PortfolioNature Communications2041-17232024-12-0115111710.1038/s41467-024-55050-yA high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogasterYuto Yoshinari0Takashi Nishimura1Taishi Yoshii2Shu Kondo3Hiromu Tanimoto4Tomoe Kobayashi5Makoto Matsuyama6Ryusuke Niwa7Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma UniversityMetabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma UniversityGraduate School of Environmental, Life, Natural Science and Technology, Okayama UniversityDepartment of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of ScienceGraduate School of Life Sciences, Tohoku UniversityDivision of Molecular Genetics, Shigei Medical Research InstituteDivision of Molecular Genetics, Shigei Medical Research InstituteLife Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of TsukubaAbstract Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to protein deficiency are well-studied, there is a significant gap in our understanding of how organisms adaptively suppress excessive protein intake. In the present study, utilizing the fruit fly, Drosophila melanogaster, we discover that the peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells in response to a high-protein diet (HPD), is vital for suppressing overconsumption of protein. Gut-derived CCHa1 is received by a small subset of enteric neurons that produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment of the CCHa1-mediated gut-enteric neuronal axis results in ammonia accumulation and a shortened lifespan under HPD conditions. Collectively, our findings unravel the crosstalk of gut hormone and neuronal pathways that orchestrate physiological responses to prevent and adapt to dietary protein overload.https://doi.org/10.1038/s41467-024-55050-y |
| spellingShingle | Yuto Yoshinari Takashi Nishimura Taishi Yoshii Shu Kondo Hiromu Tanimoto Tomoe Kobayashi Makoto Matsuyama Ryusuke Niwa A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster Nature Communications |
| title | A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster |
| title_full | A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster |
| title_fullStr | A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster |
| title_full_unstemmed | A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster |
| title_short | A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster |
| title_sort | high protein diet responsive gut hormone regulates behavioral and metabolic optimization in drosophila melanogaster |
| url | https://doi.org/10.1038/s41467-024-55050-y |
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