Regulation of Aggression by Obesity-Linked GenesTfAP-2andTwzThrough Octopamine Signaling inDrosophila

Williams, Michael J.; Goergen, Philip; Rajendran, Jayasimman; Klockars, Anica; Kasagiannis, Anna; Fredriksson, Robert; Schiöth, Helgi B.

doi:10.1534/genetics.113.158402

Cited by 37 publications

(55 citation statements)

References 62 publications

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“…We already established that Twz was necessary for TfAP-2 expression in octopaminergic neurons (Text S1, Figure S1A) [6]. To understand if Twz was necessary for the increase observed in TfAP-2 expression when flies were starved or raised on a low calorie diet, we knocked down Twz in octopaminergic neurons and performed qPCR analysis.…”

Section: Resultsmentioning

confidence: 97%

“…To determine if TfAP-2 and Twz were regulating feeding through octopamine signaling, we fed flies 3 mM of the octopamine antagonist phentolamine, a concentration known to reduce TfAP-2 OE induced hyperactivity to control levels, while not reducing the activity of controls [6]. A CAFE assay was performed to determine the total food intake and the average number of feeding bouts per fly over 24 h. While Tdc2-GAL4 +/− and TfAP-2 OE+/− control flies ate 246.4 nl (SE ±22.2) and 246.8 nl (SE ±32.9) respectively, similar to before, overexpressing TfAP-2 in octopaminergic neurons significantly increased the total food intake to 548.8 nl (SE ±66.3, P<0.005).…”

Section: Resultsmentioning

confidence: 99%

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Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

et al. 2014

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In all animals managing the size of individual meals and frequency of feeding is crucial for metabolic homeostasis. In the current study we demonstrate that the noradrenalin analogue octopamine and the cholecystokinin (CCK) homologue Drosulfakinin (Dsk) function downstream of TfAP-2 and Tiwaz (Twz) to control the number of meals in adult flies. Loss of TfAP-2 or Twz in octopaminergic neurons increased the size of individual meals, while overexpression of TfAP-2 significantly decreased meal size and increased feeding frequency. Of note, our study reveals that TfAP-2 and Twz regulate octopamine signaling to initiate feeding; then octopamine, in a negative feedback loop, induces expression of Dsk to inhibit consummatory behavior. Intriguingly, we found that the mouse TfAP-2 and Twz homologues, AP-2β and Kctd15, co-localize in areas of the brain known to regulate feeding behavior and reward, and a proximity ligation assay (PLA) demonstrated that AP-2β and Kctd15 interact directly in a mouse hypothalamus-derived cell line. Finally, we show that in this mouse hypothalamic cell line AP-2β and Kctd15 directly interact with Ube2i, a mouse sumoylation enzyme, and that AP-2β may itself be sumoylated. Our study reveals how two obesity-linked homologues regulate metabolic homeostasis by modulating consummatory behavior.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

et al. 2014

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“…It was furthermore suggested that octopamine could modulate aggressive behavior via neurons releasing the cholecystokinin-like peptide drosulfakinin (DSK) [40]. One set of neurons that express DSK are the brain IPCs [45].…”

Section: Resultsmentioning

confidence: 99%

Drosophila Insulin-Producing Cells Are Differentially Modulated by Serotonin and Octopamine Receptors and Affect Social Behavior

et al. 2014

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A set of 14 insulin-producing cells (IPCs) in the Drosophila brain produces three insulin-like peptides (DILP2, 3 and 5). Activity in IPCs and release of DILPs is nutrient dependent and controlled by multiple factors such as fat body-derived proteins, neurotransmitters, and neuropeptides. Two monoamine receptors, the octopamine receptor OAMB and the serotonin receptor 5-HT1A, are expressed by the IPCs. These receptors may act antagonistically on adenylate cyclase. Here we investigate the action of the two receptors on activity in and output from the IPCs. Knockdown of OAMB by targeted RNAi led to elevated Dilp3 transcript levels in the brain, whereas 5-HT1A knockdown resulted in increases of Dilp2 and 5. OAMB-RNAi in IPCs leads to extended survival of starved flies and increased food intake, whereas 5-HT1A-RNAi produces the opposite phenotypes. However, knockdown of either OAMB or 5-HT1A in IPCs both lead to increased resistance to oxidative stress. In assays of carbohydrate levels we found that 5-HT1A knockdown in IPCs resulted in elevated hemolymph glucose, body glycogen and body trehalose levels, while no effects were seen after OAMB knockdown. We also found that manipulations of the two receptors in IPCs affected male aggressive behavior in different ways and 5-HT1A-RNAi reduced courtship latency. Our observations suggest that activation of 5-HT1A and OAMB signaling in IPCs generates differential effects on Dilp transcription, fly physiology, metabolism and social interactions. However the findings do not support an antagonistic action of the two monoamines and their receptors in this particular system.

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“…Most of them utilize gentle aspiration to introduce pairs of males to the behavioral chambers (Dierick 2007;Wang et al 2011;Alekseyenko et al 2013). In some studies, flies are anesthetized prior to introducing them to arenas by using a brief dip of their isolation vials into an ice-water bath (Williams et al 2014), or by using CO 2 anesthesia (Yuan et al 2014). Since many studies have reported detrimental effects of CO 2 anesthesia on courtship, flight, wing movement behaviors, and on lifespan, we do not consider that further here (Gilberts 1981;Gotz and Biesinger 1985;Joachim and Curtsinger 1990).…”

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confidence: 99%

Handling alters aggression and “loser” effect formation inDrosophila melanogaster

2015

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In Drosophila, prior fighting experience influences the outcome of later contests: losing a fight increases the probability of losing second contests, thereby revealing "loser" effects that involve learning and memory. In these experiments, to generate and quantify the behavioral changes observed as consequences of losing fights, we developed a new behavioral arena that eliminates handling. We compared two commonly used fly handling procedures with this new chamber and demonstrated that handling influences aggressive behavior and prevents "loser" effect formation. In addition, we induced and observed novel aspects of learning associated with aggression such as the formation of robust winner effects.

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Regulation of Aggression by Obesity-Linked GenesTfAP-2andTwzThrough Octopamine Signaling inDrosophila

Cited by 37 publications

References 62 publications

Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

Obesity-Linked Homologues TfAP-2 and Twz Establish Meal Frequency in Drosophila melanogaster

Drosophila Insulin-Producing Cells Are Differentially Modulated by Serotonin and Octopamine Receptors and Affect Social Behavior

Handling alters aggression and “loser” effect formation inDrosophila melanogaster

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