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Published August 13, 2018 | Published + Supplemental Material
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Identification and characterization of mushroom body neurons that regulate fat storage in Drosophila


Background: In an earlier study, we identified two neuronal populations, c673a and Fru-GAL4, that regulate fat storage in fruit flies. Both populations partially overlap with a structure in the insect brain known as the mushroom body (MB), which plays a critical role in memory formation. This overlap prompted us to examine whether the MB is also involved in fat storage homeostasis. Methods: Using a variety of transgenic agents, we selectively manipulated the neural activity of different portions of the MB and associated neurons to decipher their roles in fat storage regulation. Results: Our data show that silencing of MB neurons that project into the α'β' lobes decreases de novo fatty acid synthesis and causes leanness, while sustained hyperactivation of the same neurons causes overfeeding and produces obesity. The α'β' neurons oppose and dominate the fat regulating functions of the c673a and Fru-GAL4 neurons. We also show that MB neurons that project into the γ lobe also regulate fat storage, probably because they are a subset of the Fru neurons. We were able to identify input and output neurons whose activity affects fat storage, feeding, and metabolism. The activity of cholinergic output neurons that innervating the β'2 compartment (MBON-β'2mp and MBON-γ5β'2a) regulates food consumption, while glutamatergic output neurons innervating α' compartments (MBON-γ2α'1 and MBON-α'2) control fat metabolism. Conclusions: We identified a new fat storage regulating center, the α'β' lobes of the MB. We also delineated the neuronal circuits involved in the actions of the α'β' lobes, and showed that food intake and fat metabolism are controlled by separate sets of postsynaptic neurons that are segregated into different output pathways.

Additional Information

© 2018 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Received: 26 June 2018 Accepted: 27 July 2018. Published online: 13 August 2018. We thank Yoshinori Aso for generously providing his collection of split-GAL4 lines and for advice on generating images of neurons. We also like to thank Mohammad Khajah for his editorial assistance. This work was supported by grants from the NIH (NS083874 and NS28182), and from the Della Martin Foundation to K.Z. Authors' contributions: BA-A and KZ devised the experimental plan. BA-A conducted all of the analysis of fat content and metabolism. B A-A and KZ, wrote the paper. Both authors read and approved the final manuscript. Ethics approval and consent to participate: All experimental data and analyses will be made available to the public upon acceptance for publication. Consent for publication: No mammalian subjects were used in this study. All authors consented to the author arrangement and to publication. The authors declare that they have no competing interests.

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August 19, 2023
August 19, 2023