ArticleNature communications2024
AgRP neuron cis-regulatory analysis across hunger states reveals that IRF3 mediates leptin's acute effects.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Leptin-sensitive hypothalamic Lepr+/Glp1r+ neurons limit hyperphagia and weight gain in diet-induced obesity.The EMBO journal · 2026Article
- Single-cell profiling identifies obesity-disrupted brain glucose sensing.Nature communications · 2026Article
- Maternal Separation Differentially Programs Structural and Functional Remodeling of Visceral Adipose Tissue Depots in Mice Exposed to a Post-Weaning High-Fat Diet.International journal of molecular sciences · 2026Article
- Article
- Angiotensin ATiScience · 2025Article
- Diabetes exacerbates SARS-CoV-2 replication through ineffective pulmonary interferon responses, delayed cell-mediated immunity, and disruption of leptin signaling.Frontiers in cellular and infection microbiology · 2025Article
- LCoRL Regulates Growth and Metabolism.Endocrinology · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
AgRP neurons in the arcuate nucleus of the hypothalamus (ARC) coordinate homeostatic changes in appetite associated with fluctuations in food availability and leptin signaling. Identifying the relevant transcriptional regulatory pathways in these neurons has been a priority, yet such attempts have been stymied due to their low abundance and the rich cellular diversity of the ARC. Here we generated AgRP neuron-specific transcriptomic and chromatin accessibility profiles from male mice during three distinct hunger states of satiety, fasting-induced hunger, and leptin-induced hunger suppression. Cis-regulatory analysis of these integrated datasets enabled the identification of 18 putative hunger-promoting and 29 putative hunger-suppressing transcriptional regulators in AgRP neurons, 16 of which were predicted to be transcriptional effectors of leptin. Within our dataset, Interferon regulatory factor 3 (IRF3) emerged as a leading candidate mediator of leptin-induced hunger-suppression. Measures of IRF3 activation in vitro and in vivo reveal an increase in IRF3 nuclear occupancy following leptin administration. Finally, gain- and loss-of-function experiments in vivo confirm the role of IRF3 in mediating the acute satiety-evoking effects of leptin in AgRP neurons. Thus, our findings identify IRF3 as a key mediator of the acute hunger-suppressing effects of leptin in AgRP neurons.
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