Drosophila as a diet discovery tool for treating amino acid disorders. (February 2023)

• Record Type: Journal Article
• Authors: Mele, Sarah; Martelli, Felipe; Lin, Jiayi; Kanca, Oguz; Christodoulou, John; Bellen, Hugo J.; Piper, Matthew D.W.; Johnson, Travis K.
• Is Part Of: Trends in endocrinology and metabolism. Volume 34:Number 2(2023)
• Page Start: 85
• Page End: 105
• Publication Date: 2023-02
• Subjects: amino acid -- metabolism -- inherited metabolic disease -- nutrition -- nutrigenomics; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2022.12.004
• Languages: English
• ISSNs: 1043-2760

Abstract

Highlights: Amino acid disorders (AADs) are a large group of inherited metabolic conditions that are individually rare, yet collectively affect more than one in 6500 live births. In several instances, dietary modification has had profound benefits to patient outcomes; however, most AADs lack an effective treatment. Model organisms have traditionally provided insights into disease mechanisms rather than for exploring diets of potential clinical application, because custom diets have been unavailable. The fruit fly Drosophila is well established for modelling human disease and has a fully customisable diet available, making it ideal for nutrigenomics studies. Abstract: Amino acid disorders (AADs) are a large group of rare inherited conditions that collectively impact one in 6500 live births, often resulting in rapid neurological decline and death during infancy. For several AADs, including phenylketonuria, dietary modification prevents physiological deterioration and ameliorates symptoms. Despite this remarkable potential for treatment success, dietary therapy for most AADs remains largely unexplored. Although animal models have provided novel insights into AAD mechanisms, few have been used for therapeutic diet discovery. Here, we find that of all the animal models, Drosophila is particularly well suited for nutrigenomic disease modelling, having amino acid pathways conserved with humans, exceptional genetic tractability, and the unique availability of a synthetic customisable diet.