Tanycyte-derived lactate activates astrocytic HCAR1 to modulate glutamatergic signaling and POMC neuron excitability.

ABSTRACT: Astrocytes and tanycytes play essential roles in hypothalamic metabolic sensing, yet how glial-glial communication translates metabolic cues into neuronal activity remains poorly understood. We previously demonstrated that tanycytes release lactate and that this metabolite modulates the activity of arcuate pro-opiomelanocortin (POMC) neurons. Here, we identify the lactate receptor, HCAR1, as a key mediator of tanycytes-astrocyte-neuron signaling in the arcuate nucleus. We show that HCAR1 is highly expressed in hypothalamic astrocytes and present in a subset of NPY neurons. In primary hypothalamic cultures, L-lactate, the endogenous agonist of HCAR1, elicited increases in astrocytic cytosolic Ca²⁺ and stimulated glutamate release; both effects were abolished by HCAR1 silencing us

SUBMITTER: Lopez S 

PROVIDER: S-EPMC13080002 | biostudies-literature | 2026 Apr

REPOSITORIES: biostudies-literature