Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability
elevations in neighboring astrocytes, revealing functional glial-glial communication in situ. Importantly, activation of astrocytic HCAR1 enhanced NMDA receptor-dependent slow inward currents and excitability in POMC neurons, an effect reproduced by pharmacological HCAR1 agonists and abolished by astrocytic HCAR1 silencing. Together, these findings uncover a glial metabolic relay in which tanycyte-derived lactate activates astrocytic HCAR1, promotes glutamate release, and enhances POMC neuron excitability, providing a mechanistic link between cerebrospinal fluid-borne glucose fluctuations and hypothalamic control of feeding.
Authors
- Ricardo C. Araneda (ORCID: https://orcid.org/0000-0001-8728-3063)
- Juan Carlos Sáez (ORCID: https://orcid.org/0000-0003-3811-0347)
- Walter Vásquez (ORCID: https://orcid.org/0000-0003-4113-8172)
- Vinka Azócar
- Roberto Elizondo-Vega
- Valentina Opazo-Mellado
- Vania Sepúlveda
- María de los Ángeles García-Robles
Institutions
- Instituto de Biología Molecular y Celular de Rosario (AR)
- University of Maryland, College Park (US)
- University of Valparaíso (CL)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-04-07
- DOI
- https://doi.org/10.1073/pnas.2537810123
- Primary Topic
- Regulation of Appetite and Obesity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agencia Nacional de Investigación y Desarrollo
- National Institute on Aging
- Fondo Nacional de Desarrollo Científico y Tecnológico