A glucagon-like endocrine pathway in Drosophila modulates both lipid and carbohydrate homeostasis
Open accessAbstract
The regulation of energy homeostasis is fundamental to all organisms. The Drosophila fat body serves as a repository for both triglycerides and glycogen, combining the energy storage functions of mammalian adipose and hepatic tissues, respectively. Here we show that mutation of the Drosophila adipokinetic hormone receptor (AKHR), a functional analog of the mammalian glucagon receptor, leads to abnormal accumulation of both lipid and carbohydrate. As a consequence of their obese phenotypes, AKHR mutants are markedly starvation resistant. We show that AKHR is expressed in the fat body, and, intriguingly, in a subset of gustatory neurons that mediate sweet taste. Genetic rescue experiments establish that the metabolic phenotypes arise exclusively from the fat body AKHR expression. Behavioral experiments demonstrate that AKHR mutants are neither sedentary nor hyperphagic, suggesting the metabolic abnormalities derive from a genetic propensity to retain energy stores. Taken together, our results indicate that a single endocrine pathway contributes to both lipid and carbohydrate catabolism in the Drosophila fat body.
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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 [38]
Both AKH peptide in flies and vertebrate glucagon can elicit increased glucose production by both glycogenolysis and gluconeogenesis.
“Both of these can elicit increased glucose production by both glycogenolysis and gluconeogenesis.”
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 [38]
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- Authors
- Bharucha, K. N., Tarr, P., & Zipursky, S. L.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Bharucha, K. N.
- Tarr, P.
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2008-10-01
- Volume
- 211
- Issue
- 19
- Pages
- 3103-3110
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- PMC
- PMC2714167
- OpenAlex
- W2166086263
- Cited by
- 239
- References
- 53
- Citations by year
- 2026: 15 · 2025: 10 · 2024: 18 · 2023: 9 · 2022: 24 · 2021: 21 · 2020: 18 · 2019: 12 · 2018: 19 · 2017: 14 · 2016: 20 · 2015: 11 · 2014: 17 · 2013: 3 · 2012: 12
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Experimental Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- California Institute of Regenerative Medicine
- National Institutes of Health
- U.S. Public Health Service (T32 69766)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K-12-HD 00850, K12HD000850)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- adipokinetic hormone receptor, glucagon receptor, Drosophila, fat body, lipid homeostasis, carbohydrate homeostasis, energy homeostasis, obesity, starvation resistance, gustatory neurons, sweet taste, triglyceride accumulation, glycogen, hormone signaling
- MeSH terms
- Animals, Drosophila, Fat Body, Homeostasis, Motor Activity, Neurons, Afferent, Phenotype, Starvation, Taste, Signal Transduction, Mutagenesis, Insertional, Receptors, Glucagon, Drosophila Proteins, Carbohydrate Metabolism, Lipid Metabolism
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