Energy Homeostasis Control in Drosophila Adipokinetic Hormone Mutants
Open accessAbstract
Maintenance of biological functions under negative energy balance depends on mobilization of storage lipids and carbohydrates in animals. In mammals, glucagon and glucocorticoid signaling mobilizes energy reserves, whereas adipokinetic hormones (AKHs) play a homologous role in insects. Numerous studies based on AKH injections and correlative studies in a broad range of insect species established the view that AKH acts as master regulator of energy mobilization during development, reproduction, and stress. In contrast to AKH, the second peptide, which is processed from the Akh encoded prohormone [termed "adipokinetic hormone precursor-related peptide" (APRP)] is functionally orphan. APRP is discussed as ecdysiotropic hormone or as scaffold peptide during AKH prohormone processing. However, as in the case of AKH, final evidence for APRP functions requires genetic mutant analysis. Here we employed CRISPR/Cas9-mediated genome engineering to create AKH and AKH plus APRP-specific mutants in the model insect Drosophila melanogaster. Lack of APRP did not affect any of the tested steroid-dependent processes. Similarly, Drosophila AKH signaling is dispensable for ontogenesis, locomotion, oogenesis, and homeostasis of lipid or carbohydrate storage until up to the end of metamorphosis. During adulthood, however, AKH regulates body fat content and the hemolymph sugar level as well as nutritional and oxidative stress responses. Finally, we provide evidence for a negative autoregulatory loop in Akh gene regulation.
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GnRH-like peptides affect body mass and feeding in Aplysia, while in Drosophila, both CRZ and AKH regulate carbohydrate and lipid metabolism, as well as feeding and stress response.
“In addition, GnRH-like peptides affect body mass and feeding in Aplysia (36, 37), while in Drosophila, both CRZ and AKH regulate carbohydrate and lipid metabolism (38–41), as well as feeding (41, 42) and stress response (43, 44).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [40]
In insects, CRZ signaling regulates aspects of metabolism.
“also in insects, CRZ signaling regulates both aspects of metabolism (40, 80)”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in <i>Platynereis</i> (2020) · cites this paper as [40]
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Systemic corazonin signalling modulates stress responses and metabolism in<i>Drosophila</i>
Kubrak, O. I., Lushchak, O. V., Zandawala, M., & Nässel, D. R. (2016) · Open Biology · doi:10.1098/rsob.160152 · Cited by 134 · see citing works
The evolution and nomenclature of GnRH-type and corazonin-type neuropeptide signaling systems
Zandawala, M., Tian, S., & Elphick, M. R. (2018) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2017.06.007 · Cited by 105 · see citing works
Andreatta, G., Broyart, C., Borghgraef, C., Vadiwala, K., Kozin, V., Polo, A., Bileck, A., Beets, I., Schoofs, L., Gerner, C., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910262116 · Cited by 61 · see citing works
- Authors
- Gáliková, M., Diesner, M., Klepsatel, P., Hehlert, P., Xu, Y., Bickmeyer, I., Predel, R., & Kühnlein, R. P.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- University of Cologne (DE)
- Corresponding author
- Kühnlein, Ronald P
- ORCID
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-08-14
- Volume
- 201
- Issue
- 2
- Pages
- 665-683
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC4596676
- OpenAlex
- W1832920476
- Cited by
- 206
- References
- 98
- Citations by year
- 2026: 24 · 2025: 18 · 2024: 20 · 2023: 11 · 2022: 19 · 2021: 22 · 2020: 27 · 2019: 20 · 2018: 21 · 2017: 12 · 2016: 10 · 2015: 1
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- adipokinetic hormone, energy homeostasis, Drosophila melanogaster, negative energy balance, lipid mobilization, carbohydrate mobilization, body fat content, nutritional stress response, oxidative stress response, metamorphosis, autoregulatory loop, CRISPR/Cas9 mutants
- MeSH terms
- Animals, Drosophila melanogaster, Energy Metabolism, Hemolymph, Homeostasis, Insect Hormones, Mutation, Oligopeptides, Oogenesis, Pyrrolidonecarboxylic Acid, Signal Transduction, Gene Expression Regulation, Developmental, Lipid Metabolism, CRISPR-Cas Systems
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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