Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism.
Metabolic homeostasis is coordinated through a robust network of signaling pathways acting across all tissues. A key part of this network is insulin-like signaling, which is fundamental for surviving glucose stress. Here, we show that Caenorhabditis elegans fed excess dietary glucose reduce insulin-...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-05-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3001655 |
| _version_ | 1811295014355992576 |
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| author | Ava Handley Qiuli Wu Tessa Sherry Rebecca Cornell Roger Pocock |
| author_facet | Ava Handley Qiuli Wu Tessa Sherry Rebecca Cornell Roger Pocock |
| author_sort | Ava Handley |
| collection | DOAJ |
| description | Metabolic homeostasis is coordinated through a robust network of signaling pathways acting across all tissues. A key part of this network is insulin-like signaling, which is fundamental for surviving glucose stress. Here, we show that Caenorhabditis elegans fed excess dietary glucose reduce insulin-1 (INS-1) expression specifically in the BAG glutamatergic sensory neurons. We demonstrate that INS-1 expression in the BAG neurons is directly controlled by the transcription factor ETS-5, which is also down-regulated by glucose. We further find that INS-1 acts exclusively from the BAG neurons, and not other INS-1-expressing neurons, to systemically inhibit fat storage via the insulin-like receptor DAF-2. Together, these findings reveal an intertissue regulatory pathway where regulation of insulin expression in a specific neuron controls systemic metabolism in response to excess dietary glucose. |
| first_indexed | 2024-04-13T05:27:03Z |
| format | Article |
| id | doaj.art-df5a7059536248b5957129fbf3a28a7e |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-13T05:27:03Z |
| publishDate | 2022-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-df5a7059536248b5957129fbf3a28a7e2022-12-22T03:00:34ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852022-05-01205e300165510.1371/journal.pbio.3001655Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism.Ava HandleyQiuli WuTessa SherryRebecca CornellRoger PocockMetabolic homeostasis is coordinated through a robust network of signaling pathways acting across all tissues. A key part of this network is insulin-like signaling, which is fundamental for surviving glucose stress. Here, we show that Caenorhabditis elegans fed excess dietary glucose reduce insulin-1 (INS-1) expression specifically in the BAG glutamatergic sensory neurons. We demonstrate that INS-1 expression in the BAG neurons is directly controlled by the transcription factor ETS-5, which is also down-regulated by glucose. We further find that INS-1 acts exclusively from the BAG neurons, and not other INS-1-expressing neurons, to systemically inhibit fat storage via the insulin-like receptor DAF-2. Together, these findings reveal an intertissue regulatory pathway where regulation of insulin expression in a specific neuron controls systemic metabolism in response to excess dietary glucose.https://doi.org/10.1371/journal.pbio.3001655 |
| spellingShingle | Ava Handley Qiuli Wu Tessa Sherry Rebecca Cornell Roger Pocock Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. PLoS Biology |
| title | Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. |
| title_full | Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. |
| title_fullStr | Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. |
| title_full_unstemmed | Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. |
| title_short | Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism. |
| title_sort | diet responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism |
| url | https://doi.org/10.1371/journal.pbio.3001655 |
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