Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster.
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)...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-09-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC4154645?pdf=render |
| _version_ | 1819226291621068800 |
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| author | Michael J Williams Philip Goergen Jayasimman Rajendran Galina Zheleznyakova Maria G Hägglund Emelie Perland Sonchita Bagchi Argyro Kalogeropoulou Zaid Khan Robert Fredriksson Helgi B Schiöth |
| author_facet | Michael J Williams Philip Goergen Jayasimman Rajendran Galina Zheleznyakova Maria G Hägglund Emelie Perland Sonchita Bagchi Argyro Kalogeropoulou Zaid Khan Robert Fredriksson Helgi B Schiöth |
| author_sort | Michael J Williams |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T10:23:10Z |
| format | Article |
| id | doaj.art-74fc0e4875c54ec2bbc42e889480636e |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T10:23:10Z |
| publishDate | 2014-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-74fc0e4875c54ec2bbc42e889480636e2022-12-21T17:50:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042014-09-01109e100449910.1371/journal.pgen.1004499Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster.Michael J WilliamsPhilip GoergenJayasimman RajendranGalina ZheleznyakovaMaria G HägglundEmelie PerlandSonchita BagchiArgyro KalogeropoulouZaid KhanRobert FredrikssonHelgi B SchiöthIn 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.http://europepmc.org/articles/PMC4154645?pdf=render |
| spellingShingle | Michael J Williams Philip Goergen Jayasimman Rajendran Galina Zheleznyakova Maria G Hägglund Emelie Perland Sonchita Bagchi Argyro Kalogeropoulou Zaid Khan Robert Fredriksson Helgi B Schiöth Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. PLoS Genetics |
| title | Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. |
| title_full | Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. |
| title_fullStr | Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. |
| title_full_unstemmed | Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. |
| title_short | Obesity-linked homologues TfAP-2 and Twz establish meal frequency in Drosophila melanogaster. |
| title_sort | obesity linked homologues tfap 2 and twz establish meal frequency in drosophila melanogaster |
| url | http://europepmc.org/articles/PMC4154645?pdf=render |
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