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The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster

Author

Listed:
  • Yuto Yoshinari

    (University of Tsukuba
    University of Tsukuba)

  • Hina Kosakamoto

    (The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research)

  • Takumi Kamiyama

    (University of Tsukuba)

  • Ryo Hoshino

    (University of Tsukuba)

  • Rena Matsuoka

    (University of Tsukuba)

  • Shu Kondo

    (National Institute of Genetics)

  • Hiromu Tanimoto

    (Tohoku University)

  • Akira Nakamura

    (Kumamoto University
    Kumamoto University)

  • Fumiaki Obata

    (University of Tsukuba
    The University of Tokyo
    RIKEN Center for Biosystems Dynamics Research
    Kyoto University)

  • Ryusuke Niwa

    (University of Tsukuba
    AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku)

Abstract

The enteroendocrine cell (EEC)-derived incretins play a pivotal role in regulating the secretion of glucagon and insulins in mammals. Although glucagon-like and insulin-like hormones have been found across animal phyla, incretin-like EEC-derived hormones have not yet been characterised in invertebrates. Here, we show that the midgut-derived hormone, neuropeptide F (NPF), acts as the sugar-responsive, incretin-like hormone in the fruit fly, Drosophila melanogaster. Secreted NPF is received by NPF receptor in the corpora cardiaca and in insulin-producing cells. NPF-NPFR signalling resulted in the suppression of the glucagon-like hormone production and the enhancement of the insulin-like peptide secretion, eventually promoting lipid anabolism. Similar to the loss of incretin function in mammals, loss of midgut NPF led to significant metabolic dysfunction, accompanied by lipodystrophy, hyperphagia, and hypoglycaemia. These results suggest that enteroendocrine hormones regulate sugar-dependent metabolism through glucagon-like and insulin-like hormones not only in mammals but also in insects.

Suggested Citation

  • Yuto Yoshinari & Hina Kosakamoto & Takumi Kamiyama & Ryo Hoshino & Rena Matsuoka & Shu Kondo & Hiromu Tanimoto & Akira Nakamura & Fumiaki Obata & Ryusuke Niwa, 2021. "The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25146-w
    DOI: 10.1038/s41467-021-25146-w
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    Cited by:

    1. Olga Kubrak & Takashi Koyama & Nadja Ahrentløv & Line Jensen & Alina Malita & Muhammad T. Naseem & Mette Lassen & Stanislav Nagy & Michael J. Texada & Kenneth V. Halberg & Kim Rewitz, 2022. "The gut hormone Allatostatin C/Somatostatin regulates food intake and metabolic homeostasis under nutrient stress," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Junjun Gao & Song Zhang & Pan Deng & Zhigang Wu & Bruno Lemaitre & Zongzhao Zhai & Zheng Guo, 2024. "Dietary L-Glu sensing by enteroendocrine cells adjusts food intake via modulating gut PYY/NPF secretion," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

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