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Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin Secretion
Open accessAbstract
In Drosophila the fat body (FB), a functional analog of the vertebrate adipose tissue, is the 'nutrient sensor' that conveys the nutrient status to the insulin producing cells (IPCs) in the fly brain to release insulin-like peptides (Dilps). Dilp secretion in turn regulates energy balance and promotes systemic growth. We identify Unpaired2 (Upd2), a protein with similarities to type I cytokines, as a secreted factor produced by the FB in the ‘fed’ state. When upd2 function is perturbed specifically in the FB, it results in a systemic reduction in growth and alters energy metabolism. Upd2 activates JAK/STAT signaling in a population of GABAergic neurons that project onto the IPCs. This activation relieves the inhibitory tone of the GABAergic neurons on the IPCs, resulting in the secretion of Dilps. Strikingly, we find that human Leptin, can rescue the upd2 mutant phenotypes, suggesting that Upd2 is the functional homolog of Leptin.
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Cites
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Central nervous system control of food intake and body weight
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Cited by
The Drosophila blood-brain barrier: development and function of a glial endothelium
Limmer, S., Weiler, A., Volkenhoff, A., Babatz, F., & Klämbt, C. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00365 · Cited by 214
Tsao, C.-H., Chen, C.-C., Lin, C.-H., Yang, H.-Y., & Lin, S. (2018) · eLife · doi:10.7554/elife.35264 · Cited by 214
Eat to reproduce: a key role for the insulin signaling pathway in adult insects
Badisco, L., Van Wielendaele, P., & Vanden Broeck, J. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00202 · Cited by 173
Suppression of Insulin Production and Secretion by a Decretin Hormone
Alfa, R. W., Park, S., Skelly, K.-R., Poffenberger, G., Jain, N., Gu, X., Kockel, L., Wang, J., Liu, Y., Powers, A. C., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.01.006 · Cited by 150
Systemic corazonin signalling modulates stress responses and metabolism in Drosophila
Kubrak, O. I., Lushchak, O. V., Zandawala, M., & Nässel, D. R. (2016) · Open Biology · doi:10.1098/rsob.160152 · Cited by 134
Metadata
- Authors
- Rajan, A., & Perrimon, N.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 151
- Issue
- 1
- Pages
- 123-137
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2148070562
- Cited by
- 498
- References
- 5
- FWCI
- 13.09
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Rajan, A., & Perrimon, N. (2012). Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin Secretion. Cell. https://doi.org/10.1016/j.cell.2012.08.019
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