1. Identifying potential dietary treatments for inherited metabolic disorders using Drosophilanutrigenomics
- Author
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Martelli, Felipe, Lin, Jiayi, Mele, Sarah, Imlach, Wendy, Kanca, Oguz, Barlow, Christopher K., Paril, Jefferson, Schittenhelm, Ralf B., Christodoulou, John, Bellen, Hugo J., Piper, Matthew D.W., and Johnson, Travis K.
- Abstract
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 Drosophilaamino 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 Drosophilaas a valuable tool for nutrigenomic studies for informing potential dietary therapies.
- Published
- 2024
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