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Genetic variation of macronutrient tolerance in Drosophila melanogaster

Author

Listed:
  • E. Havula

    (The University of Sydney
    The University of Sydney
    University of Helsinki)

  • S. Ghazanfar

    (The University of Sydney
    University of Cambridge)

  • N. Lamichane

    (University of Helsinki
    University of Helsinki)

  • D. Francis

    (The University of Sydney)

  • K. Hasygar

    (University of Helsinki
    University of Helsinki)

  • Y. Liu

    (University of Helsinki
    University of Helsinki)

  • L. A. Alton

    (Monash University)

  • J. Johnstone

    (Monash University)

  • E. J. Needham

    (The University of Sydney
    The University of Sydney)

  • T. Pulpitel

    (The University of Sydney)

  • T. Clark

    (The University of Sydney)

  • H. N. Niranjan

    (The University of Sydney)

  • V. Shang

    (The University of Sydney)

  • V. Tong

    (The University of Sydney)

  • N. Jiwnani

    (The University of Sydney)

  • G. Audia

    (The University of Sydney)

  • A. N. Alves

    (Monash University)

  • L. Sylow

    (University of Copenhagen
    University of Copenhagen)

  • C. Mirth

    (Monash University)

  • G. G. Neely

    (The University of Sydney
    The University of Sydney)

  • J. Yang

    (The University of Sydney
    The University of Sydney)

  • V. Hietakangas

    (University of Helsinki
    University of Helsinki)

  • S. J. Simpson

    (The University of Sydney
    The University of Sydney)

  • A. M. Senior

    (The University of Sydney
    The University of Sydney
    The University of Sydney)

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.

Suggested Citation

  • 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., 2022. "Genetic variation of macronutrient tolerance in Drosophila melanogaster," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29183-x
    DOI: 10.1038/s41467-022-29183-x
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    References listed on IDEAS

    as
    1. Alejo Efeyan & William C. Comb & David M. Sabatini, 2015. "Nutrient-sensing mechanisms and pathways," Nature, Nature, vol. 517(7534), pages 302-310, January.
    2. Ida Moltke & Niels Grarup & Marit E. Jørgensen & Peter Bjerregaard & Jonas T. Treebak & Matteo Fumagalli & Thorfinn S. Korneliussen & Marianne A. Andersen & Thomas S. Nielsen & Nikolaj T. Krarup & Ane, 2014. "A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes," Nature, Nature, vol. 512(7513), pages 190-193, August.
    3. Hiroko Ohki-Hamazaki & Kei Watase & Kazutoshi Yamamoto & Hiroo Ogura & Mariko Yamano & Kazuyuki Yamada & Hiroshi Maeno & Junko Imaki & Sakae Kikuyama & Etsuko Wada & Keiji Wada, 1997. "Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity," Nature, Nature, vol. 390(6656), pages 165-169, November.
    4. Jiro Hirosumi & Gürol Tuncman & Lufen Chang & Cem Z. Görgün & K. Teoman Uysal & Kazuhisa Maeda & Michael Karin & Gökhan S. Hotamisligil, 2002. "A central role for JNK in obesity and insulin resistance," Nature, Nature, vol. 420(6913), pages 333-336, November.
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