Genetic variation of macronutrient tolerance in Drosophila melanogaster

Havula, E., Ghazanfar, S., Lamichane, N., Francis, D., Hasygar, K., Liu, Y., Alton, L.A., Johnstone, J., Needham, E.J., Pulpitel, T., Clark, T., Niranjan, H.N., Shang, V., Tong, V., Jiwnani, N., Audia, G., Alves, A.N., Sylow, L., Mirth, C., Neely, G.G., Yang, J., Hietakangas, V., Simpson, S.J., and Senior, A.M. (2022) Genetic variation of macronutrient tolerance in Drosophila melanogaster. Nature Communications, 13. 1637.

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Carbohydrates, proteins and lipids are essential nutrients to all animals; however, closely related species, populations, and individuals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster, often considered a "dietary generalist", displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8, Pkn and Eip75B. We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailless, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.

Item ID: 73618
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Funders: Australian Research Council (ARC), National Health and Medical Research Council of Australia (NHMRC)
Projects and Grants: ARC Discovery Project (DP180103925), ARC (FT170100259), ARC Discovery Early Career Award (DE180101520)
Date Deposited: 01 Jun 2022 00:17
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310207 Statistical and quantitative genetics @ 50%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3210 Nutrition and dietetics > 321003 Nutrigenomics and personalised nutrition @ 25%
31 BIOLOGICAL SCIENCES > 3101 Biochemistry and cell biology > 310103 Cell metabolism @ 25%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 100%
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