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Identifying potential dietary treatments for inherited metabolic disorders using Drosophila nutrigenomics
oleh: Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K. Barlow, Jefferson Paril, Ralf B. Schittenhelm, John Christodoulou, Hugo J. Bellen, Matthew D.W. Piper, Travis K. Johnson
Format: | Article |
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Diterbitkan: | Elsevier 2024-03-01 |
Deskripsi
Summary: Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, behavior, and lifelong fly survival, thus providing a basis for further study into the pathogenic mechanisms involved in this disorder. Our work highlights the diet-sensitive nature of metabolic disorders and establishes Drosophila as a valuable tool for nutrigenomic studies for informing potential dietary therapies.