Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism
Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism
SUMMARY To maintain metabolic homeostasis, the nervous system must adapt and respond to an ever-changing environment. Transcription factors are key drivers of this adaptation, eliciting gene expression changes that can alter neuronal activity. Here we show in Caenorhabditis elegans that the terminal selector transcription factor ETS-5 not only establishes the identity of the BAG sensory neurons, but is re-purposed to shape the functional output of the BAG neurons post-mitotically. We find that ETS-5 directly regulates the expression of INS-1, an insulin-like peptide, in the BAG sensory neurons. INS-1 expression in the BAG neurons, and not in other INS-1-expressing neurons, decreases intestinal lipid levels and promotes foraging behaviour. Using in vivo analysis, we show that elevated intestinal lipid stores, driven by a high glucose diet, downregulates ETS-5-driven expression of INS-1. Together, our data reveal an inter-tissue regulatory loop by which a single neuron can control systemic metabolism, and that the activity of this neuron is modulated by the metabolic state of the organism.
Sherry Tessa、Handley Ava、Pocock Roger、Wu Qiuli
Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash UniversityDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash UniversityDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash UniversityDevelopment and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University||Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School of Southeast University
基础医学生理学分子生物学
Metabolic homeostasisgut-brain signallingneuroplasticityforagingbehavioural statestranscription factorinsulinneuropeptide
Sherry Tessa,Handley Ava,Pocock Roger,Wu Qiuli.Diet-responsive Transcriptional Regulation of Insulin in a Single Neuron Controls Systemic Metabolism[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/751339.点此复制
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