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

Yuto Yoshinari, Hina Kosakamoto, Takumi Kamiyama, Ryo Hoshino, Rena Matsuoka, Shu Kondo, Hiromu Tanimoto, Akira Nakamura, Fumiaki Obata and Ryusuke Niwa ()
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Yuto Yoshinari: University of Tsukuba
Hina Kosakamoto: The University of Tokyo
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
Fumiaki Obata: University of Tsukuba
Ryusuke Niwa: University of Tsukuba

Nature Communications, 2021, vol. 12, issue 1, 1-21

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-25146-w

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