Adenosine transmission from hypothalamic tanycytes to AGRP/NPY neurons regulates energy homeostasis.

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ID: 282150
2025
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Abstract
Tanycytes are a pivotal component of the hypothalamic network that controls energy homeostasis. Despite their importance, the regulatory mechanisms governing tanycyte-neuron interactions in response to metabolic signals remain unexplored. Here we report that adenosine signaling between tanycytes and AGRP/NPY neurons is crucial for tanycytic metabolic regulation mediated by translocator protein 18 kDa (TSPO). Tanycyte-specific Tspo-knockout mice displayed reduced food consumption and weight loss associated with the downregulation of Agrp and Npy expression under high-fat diet feeding. Tspo-deficient tanycytes had elevated levels of intracellular ATP, which was released via connexin 43 hemichannels and extracellularly converted into adenosine by tanycytic ectonucleotidases. The adenosine signal was perceived by adenosine A1 receptors on adjacent AGRP/NPY neurons, reducing ERK phosphorylation, which in turn downregulated Agrp and Npy expression. Our findings underscore the anorexic role of adenosine as a gliotransmitter in the intricate communication between tanycytes and neurons for regulating appetite and body weight.
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kim2025adenosine Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Kim, Nayoun; Kim, Seolsong; Park, Seokjae; Kim, Eun-Kyoung
Journal experimental & molecular medicine
Year 2025
DOI
10.1038/s12276-025-01449-6
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