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., Senior, A.M. (2022). Genetic variation of macronutrient tolerance in Drosophila melanogaster.  Nat. Commun. 13(1): 1637.

FBrf0253029

Research paper

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.

PMC8960806 (PMC) (EuropePMC)