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Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism.

ABSTRACT: 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.

SUBMITTER: Handley A

PROVIDER: S-EPMC9162364 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Diet-responsive transcriptional regulation of insulin in a single neuron controls systemic metabolism.

Handley Ava A Wu Qiuli Q Sherry Tessa T Cornell Rebecca R Pocock Roger R

PLoS biology 20220520 5

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 a ...[more]

PMID: 35594303

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