TY - JOUR
T1 - Genetic variation of macronutrient tolerance in Drosophila melanogaster
AU - Havula, E.
AU - Ghazanfar, S.
AU - Lamichane, N.
AU - Francis, D.
AU - Hasygar, K.
AU - Liu, Y.
AU - Alton, L. A.
AU - Johnstone, J.
AU - Needham, E. J.
AU - Pulpitel, T.
AU - Clark, T.
AU - Niranjan, H. N.
AU - Shang, V.
AU - Tong, V.
AU - Jiwnani, N.
AU - Audia, G.
AU - Alves, A. N.
AU - Sylow, L.
AU - Mirth, C.
AU - Neely, G. G.
AU - Yang, J.
AU - Hietakangas, V.
AU - Simpson, S. J.
AU - Senior, A. M.
N1 - Funding Information:
We thank Hugo Stocker and Ernst Hafen for reagents, Hiroko Sano for providing the CCHa2 mutant fly line, and John O’Sullivan and Mengbo Li for help with the human T2D knowledge portal. E.H. is supported by the Finnish Diabetes Research Foundation, the Orion Research Foundation and the Maud Kuistila Foundation. S.G. is supported by a Royal Society Newton International Fellowship (NIF\R1\181950). L.A.A. is supported by the Australian Research Council Discovery Project (DP180103925). V.H. is supported by the Novo Nordisk Foundation Grant NNF19OC0057478 and the Sigrid Juselius Foundation. C.M. is supported by the Australian Research Council (FT170100259). A.M.S. was supported by an Australian Research Council Discovery Early Career Award (DE180101520). This work was majority funded by a grant from National Health and Medical Research Council of Australia, which was awarded to Prof. David James who conceived the original project and supervised most of the component studies.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85127267170&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-29183-x
DO - 10.1038/s41467-022-29183-x
M3 - Article
C2 - 35347148
AN - SCOPUS:85127267170
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1637
ER -