Sayak Banerjee, Amity University Kolkata
It is a necessity for all organisms for preserving energy homeostasis whenever there is a response to nutrient availability. They coordinate systemic energy homeostasis for regulating the balance of catabolism and anabolism through humoral factors. Insulin and counter-regulatory hormones like glucagon have been observed to take part as humoral factors to nutrient availability. Insulin induces the circulation of carbohydrate clearance promoting fat storage, whereas glucagon increases the release of carbohydrates into circulation.
Additionally, the intestine plays a key role in maintaining systemic energy homeostasis. The enteroendocrine cells (EEC) secrete multiple hormones called incretins which activate the secretion of insulin and glucagon. Although hormones similar to insulin and glucagon have been identified across the animal kingdom, EEC-derived incretin-like hormones are yet to be discovered. Recently, scientists at the University of Tsukuba have reported that the midgut-derived hormone, neuropeptide F (NPF), could carry out this complex role in the fruit fly, Drosophila melanogaster.
NPF and its role in the fruit fly
Despite being structurally different from its mammalian homolog, NPF is secreted from midgut EECs in response to dietary nutrients. It is attached to the NPF receptor (NPRF) that is present in a specialized endocrine organ, corpora cardiaca (CC), and insulin-producing cells (IPC). The researchers demonstrated that NPF signals NPRF and triggers IPC in the insect brain for the suppression of glucagon-like hormone. Simultaneously, it also enhances the production of an insulin-like peptide. This leads to the increase in glucose level in the hemolymph and stimulates lipid accretion in body fat.
The research team had previously discovered the reproductive role of NPF in the fruit fly. They were curious regarding its function in other biological processes, especially in systemic energy homeostasis. Their approach was to produce mutant flies of specific gene knockout strain and knock-in strains by the application of advanced genetic engineering. They had employed high-tech laboratory methods to determine the genetic and molecular signaling pathways along with fundamental cellular mechanisms.
The scientists observed that the absence of midgut or impaired NPF/NPFR signaling in the fruit fly generated metabolic disorders. This resembled the incretin loss in mammals leading to hypoglycemia, hyperphagia (overfeeding), and lipidodystrophy (loss of healthy fat). They also found that brain-specific NPF knockdown is not a phenocopy of midgut-specific NPF knockdown. This entails that the functions of the brain and midgut NPF are physiologically different. Moreover, the most significant finding is that the brain-derived NPF is orexigenic in function, distinct from the anorexigenic function of midgut-derived NPF. The reason behind the abnormal feeding behavior and reduced growth in numerous insects is disordered NPF/NPRF signaling.
Significance of incretin-like EEC hormones in the fruit fly
D. melanogaster is a potent study model for revealing the function of incretin-like EEC hormones in systemic metabolisms in organisms. This is because of the effortlessness of tissue-specific genetic engineering along with the evolutionary conservation of the signaling pathways regulating systemic energy homeostasis. This study has focused on the principal resemblance in the sugar-dependent metabolic processes between mammals and invertebrates. Future studies are required for a better understanding of the function of incretins. This may open the doors for therapeutic approaches for the disorders linked with their abnormalities like type 2 diabetes and obesity.
Also read: Is tryptophan deficiency associated with inflammation?
Reference:
- Yoshinari, Y., Kosakamoto, H., Kamiyama, T., Hoshino, R., Matsuoka, R., Kondo, S., Tanimoto, H., Nakamura, A., Obata, F., & Niwa, R. (2021). The sugar-responsive enteroendocrine neuropeptide F regulates lipid metabolism through glucagon-like and insulin-like hormones in Drosophila melanogaster. Nature Communications, 12(1), 4818. https://doi.org/10.1038/s41467-021-25146-w
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Author info:
Sayak Banerjee is a 3rd-year Biotechnology Engineering Student with a great interest in Immunology and Molecular genetics. He is a creative scientific writer in Bioxone with an inclination towards gaining knowledge regarding vast sections of Biotechnology and emphasizing himself in various wet lab skills.
Publications:
- https://bioxone.in/news/worldnews/car-t-cells-scientists-discover-on-off-switches-for-cell-immunotherapy/
- https://bioxone.in/news/worldnews/neutrophil-derived-nanovesicles-a-novel-drug-delivery-system/
- https://bioxone.in/news/worldnews/pig-to-human-heart-transplantation-a-solution-to-the-rarity-of-donor-organs/
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