Drosophila as a diet discovery tool for treating amino acid disorders

Mele, Sarah; Martelli, Felipe; Lin, Jizhen; Kanca, Oguz; Christodoulou, John; Bellen, Hugo J.; Piper, Matthew D.W.; Johnson, Travis K.

doi:10.1016/j.tem.2022.12.004

Cited by 6 publications

(8 citation statements)

References 129 publications

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“…In addition to its energetic role, AKG is involved in the metabolism of amino acids (Bayliak & Lushchak, 2021; Mele et al, 2023). Therefore, we determined the activity of glutamate dehydrogenase (GDH), whose substrate is AKG.…”

Section: Discussionmentioning

confidence: 99%

Alpha‐ketoglutarate supplementation in long‐lived Drosophila melanogaster: Impact on lifespan and metabolic responses

Demianchuk,

Lylyk,

Balatskiy

et al. 2024

Arch Insect Biochem Physiol

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Studies on antiaging remedies in insect models sometimes show discrepancies in results. These discrepancies could be explained by different responses of short‐ and long‐lived strains on the antiaging remedies. The purpose of the study was to test whether life‐prolonging effects of alpha‐ketoglutarate (AKG), observed in nematodes and fruit flies, would be reproduced in long‐lived Drosophila melanogaster flies. Lifespan was assayed in flies kept in demographic cages. Fecundity, proportion of flies capable of negative geotaxis, starvation resistance, time of heat coma onset, levels of triacyglycerols, body glucose, glycogen, activities of glutamate dehydrogenase, catalase, glutathione‐S‐transferase, hexokinase, phosphofructokinase, pyruvate kinase, lactate, and glutamate dehydrogenases were assessed. Dietary AKG did not affect fly lifespan on the diet with 5% yeast and 5% sucrose (5Y:5S) and on the diet with 9% yeast and 1% sucrose (9Y:1S), but increased lifespan on the low‐protein diet (1Y:9S). Twenty‐five‐day‐old female flies fed a 5Y:5S diet with 10 mM AKG for 3 weeks, did not differ from the control group (without AKG) in climbing activity, resistance to heat stress, and starvation. The levels of glucose and glycogen were unaffected but the levels of triacylglycerols were lower in AKG‐fed female flies. No differences in activities of glycolytic enzymes, NADPH‐producing enzymes, glutamate dehydrogenase, oxygen consumption, and levels of oxidative stress markers were observed between the control and AKG‐fed flies. However, AKG‐fed flies had lower activities of catalase and glutathione‐S‐transferase. These results suggest that potential antiaging remedies, such as AKG, may not extend lifespan in long‐living organisms despite influencing several metabolic parameters.

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Section: Discussionmentioning

confidence: 99%

Alpha‐ketoglutarate supplementation in long‐lived Drosophila melanogaster: Impact on lifespan and metabolic responses

Demianchuk,

Lylyk,

Balatskiy

et al. 2024

Arch Insect Biochem Physiol

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“…For example, human disorders such as Phenylketonuria manifest with rapid neurological decline prior to adulthood mitigated by a custom diet with single aa restriction that drastically improves health outcomes 9 . However, the majority of metabolic disorders lack therapeutic diets 8 . To demonstrate the potential of our diet as a tool to find new dietary treatments, we applied it in a model of human Branched Chain Amino Acid (BCAA) Transaminase ( BCAT2 ) deficiency, a rare disorder associated with developmental delay, intellectual disability, seizures, and movement defects 10 .…”

Section: Mainmentioning

confidence: 99%

“…1j), restored fat levels, and enhanced body mass, without compromising adult lifespan. A synthetic diet on which Drosophila can be raised is particularly valuable in the modelling of human metabolic disorders, where phenotypic abnormalities often manifest prior to adulthood 8 . For example, human disorders such as Phenylketonuria manifest with rapid neurological decline prior to adulthood mitigated by a custom diet with single aa restriction that drastically improves health outcomes 9 .…”

mentioning

confidence: 99%

A defined diet for pre-adultDrosophila melanogaster

Martelli,

Quig,

Mele

et al. 2023

Preprint

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Drosophilamelanogaster is unique among animal models because it has a fully defined synthetic diet available to study nutrient-gene interactions. However, use of this diet is limited to adult studies due to impaired larval development and survival. Here, we provide an adjusted formula that improves larval growth, development rate, and rescues survival. We demonstrate its use for exploring pre-adult diet compositions of therapeutic potential in a model of an inherited metabolic disorder.

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“…For example, over 30 mouse models have been created and used to dissect AAD mechanisms. 13 Very few of these studies, however, have focused on evaluating dietary treatments because of the cost and time associated with complex large-scale feeding trials with mice and the challenges associated with manufacturing nutrient-varied semi-synthetic diets.…”

Section: Introductionmentioning

confidence: 99%

“…An animal well suited to study nutrigenetic interactions in disease models is the fruit fly Drosophila melanogaster . 13 In addition to their genetic tractability, a key benefit is that Drosophila can be reared quickly, permitting large cohorts of genetically similar individuals to be surveyed across an array of different conditions at a relatively low cost. 14 These features, coupled with the recent development of a defined fully synthetic diet that allows for the complete manipulation of its composition, 15 enable exploration of genotype-nutrient interactions at high resolution.…”

Section: Introductionmentioning

confidence: 99%

Drosophila as a diet discovery tool for treating amino acid disorders

Cited by 6 publications

References 129 publications

Alpha‐ketoglutarate supplementation in long‐lived Drosophila melanogaster: Impact on lifespan and metabolic responses

Alpha‐ketoglutarate supplementation in long‐lived Drosophila melanogaster: Impact on lifespan and metabolic responses

A defined diet for pre-adultDrosophila melanogaster

Identifying potential dietary treatments for inherited metabolic disorders using Drosophila nutrigenomics

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