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The Drosophila ETV5 homologue Ets96B modulates feeding behavior
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Recent genome-wide association studies (GWAS) have linked the PEA3-family member ets variant 5 (ETV5) to BMI and obesity, yet how this gene regulates metabolic homeostasis is still not clear. The PEA3-family was found to be remarkably conserved and present in species from Drosophila melanogaster to humans. The Drosophila PEA3-family homologue Ets96B is expressed in both the larval and adult central nervous system and, similar to mammalian ETV5, is highly expressed in the testis. In the current study we demonstrate that the obesity-linked homologue Ets96B regulates feeding behavior, as well as lipid storage in adult flies. Furthermore, we demonstrate this is a developmental phenotype. Of notable interest, when Ets96B was knocked down in the entire CNS or specifically in Ets96B expressing cells from embryogenesis, feeding behavior and lipid storage phenotypes were observed; yet when Ets96B was specifically knocked down in the adult CNS there was no effect on feeding, while an opposite effect on lipid storage was revealed. From these data we speculate that loss of Ets96B may disrupt CNS development, leading to metabolic homeostatic phenotypes.

National Category
Neurosciences
Research subject
Medical Science
Identifiers
URN: urn:nbn:se:uu:diva-223808OAI: oai:DiVA.org:uu-223808DiVA: diva2:714277
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-06-30
In thesis
1. Non-caloric regulation of food intake
Open this publication in new window or tab >>Non-caloric regulation of food intake
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Food intake is shaped by environmental, endocrine, metabolic, and reward-related signals. A change in appetite is an outcome of integration of the relevant external and internal stimuli. While the main purpose of eating is to reverse a negative energy balance, mechanisms protecting homeostasis change appetite for other reasons. This thesis examines the role of select brain mechanisms in regulating consumption driven by aspects other than energy.

In paper I, an increased percentage of c-Fos positive OT neurons was observed after mice ingested sucrose, while no change was found after Intralipid intake. Given a choice between isocaloric sugar and Intralipid solutions, mice injected with an OT receptor antagonist increase their preference for sucrose, while total calorie intake remains unchanged, suggesting that OT prevents overconsumption of sugar.

Paper II addresses whether MCH, which has anxiolytic properties and mediates reward-motivated feeding, has the ability to alleviate conditioned taste aversion in rats. We found that while mRNA expression of MCH and its receptor are changed in aversive animals, central injections of MCH do not prevent the acquisition of aversion, nor do they affect the rate of extinction of the taste aversion.

Paper III describes evidence that the N/OFQ system facilitates food intake by alleviating aversive responsiveness. Blocking the NOP receptor delays extinction of aversion and reduces food intake in hungry rats.

Paper IV reports that leucine ingestion increases mRNA expression levels of genes known to mediate reward, as well as orexigenic gene expression in the nucleus accumbens (Nacc), a key component of the reward circuit. Adding leucine to drinking water increases activity of the reward system, which possibly contributes to the pleasure of consumption.

A separate approach using Drosophila melanogaster is introduced in paper V which provides evidence that knocking down the gene for the transcription factor Ets96B during development results in a simultaneous disruption in sleep patterns and appetite, thus highlighting the interplay between these physiological parameters.

We conclude that OT, MCH, N/OFQ and Ets96B belong to mechanisms regulating food intake for reasons other than energy balance. Composition of food and negative associations with diets affect neural networks controlling appetite.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 54 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1007
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-223809 (URN)978-91-554-8966-3 (ISBN)
Public defence
2014-06-13, B:21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2014-05-23 Created: 2014-04-25 Last updated: 2014-06-30

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