Genetic variation of macronutrient tolerance in Drosophila melanogaster

E Havula; S Ghazanfar; N Lamichane; D Francis; K Hasygar; Y Liu; L A Alton; J Johnstone; E J Needham; T Pulpitel; T Clark; H N Niranjan; V Shang; V Tong; N Jiwnani; G Audia; A N Alves; Lykke Sylow; C Mirth; Greg G Neely; J Yang; V Hietakangas; S J Simpson; Alistair M Senior

doi:10.1038/s41467-022-29183-x

Genetic variation of macronutrient tolerance in Drosophila melanogaster

E Havula^*, S Ghazanfar, N Lamichane, D Francis, K Hasygar, Y Liu, L A Alton, J Johnstone, E J Needham, T Pulpitel, T Clark, H N Niranjan, V Shang, V Tong, N Jiwnani, G Audia, A N Alves, Lykke Sylow, C Mirth, Greg G NeelyJ Yang, V Hietakangas, S J Simpson, Alistair M Senior^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

13 Citations (Scopus)

26 Downloads (Pure)

Abstract

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.

Original language	English
Article number	1637
Journal	Nature Communications
Volume	13
Number of pages	16
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-022-29183-x
Publication status	Published - 2022

Bibliographical note

Access to Document

10.1038/s41467-022-29183-xLicence: CC BY

Havula et al_Nature Communications_2022_Vol 13_e1637Final published version, 3.35 MBLicence: CC BY

Cite this

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., ... Senior, A. M. (2022). Genetic variation of macronutrient tolerance in Drosophila melanogaster. Nature Communications, 13, [1637]. https://doi.org/10.1038/s41467-022-29183-x

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, Lykke; Mirth, C; Neely, Greg G; Yang, J; Hietakangas, V; Simpson, S J; Senior, Alistair M.

In: Nature Communications, Vol. 13, 1637, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Havula, E, Ghazanfar, S, Lamichane, N, Francis, D, Hasygar, K, Liu, Y, Alton, LA, Johnstone, J, Needham, EJ, Pulpitel, T, Clark, T, Niranjan, HN, Shang, V, Tong, V, Jiwnani, N, Audia, G, Alves, AN, Sylow, L, Mirth, C, Neely, GG, Yang, J, Hietakangas, V, Simpson, SJ & Senior, AM 2022, 'Genetic variation of macronutrient tolerance in Drosophila melanogaster', Nature Communications, vol. 13, 1637. https://doi.org/10.1038/s41467-022-29183-x

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, Lykke ; Mirth, C ; Neely, Greg G ; Yang, J ; Hietakangas, V ; Simpson, S J ; Senior, Alistair M. / Genetic variation of macronutrient tolerance in Drosophila melanogaster. In: Nature Communications. 2022 ; Vol. 13.

@article{9fa69b335bb74034af0806ca3e0ed9b9,

title = "Genetic variation of macronutrient tolerance in Drosophila melanogaster",

abstract = "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.",

author = "E Havula and S Ghazanfar and N Lamichane and D Francis and K Hasygar and Y Liu and Alton, {L A} and J Johnstone and Needham, {E J} and T Pulpitel and T Clark and Niranjan, {H N} and V Shang and V Tong and N Jiwnani and G Audia and Alves, {A N} and Lykke Sylow and C Mirth and Neely, {Greg G} and J Yang and V Hietakangas and Simpson, {S J} and Senior, {Alistair M}",

note = "{\textcopyright} 2022. The Author(s).",

year = "2022",

doi = "10.1038/s41467-022-29183-x",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

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, Lykke

AU - Mirth, C

AU - Neely, Greg G

AU - Yang, J

AU - Hietakangas, V

AU - Simpson, S J

AU - Senior, Alistair M

PY - 2022

Y1 - 2022

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.

U2 - 10.1038/s41467-022-29183-x

DO - 10.1038/s41467-022-29183-x

M3 - Journal article

C2 - 35347148

VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1637

ER -