Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons

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Lhomme, Tori | Clasadonte, Jerome | 1&, Monica, Imbernon | Fernandois, Daniela | Sauve, Florent | Caron, Emilie | da Silva Lima, Natalia | Heras, Violeta | Martinez-Corral, Ines | Mueller-Fielitz, Helge | Rasika, S | Schwaninger, Markus | Nogueiras, Ruben | Prevot, Vincent

Edité par CCSD ; American Society for Clinical Investigation -

International audience. Hypothalamic glucose sensing enables an organism to match energy expenditure and food intake to circulating levels of glucose, the main energy source of the brain. Here, we established that tanycytes of the hypothalamic arcuate nucleus, specialized glia that line the wall of the third ventricle, convert brain glucose supplies into lactate that they transmit through monocarboxylate transporters to arcuate proopiomelanocortin neurons, which integrate this signal to drive their activity and to adapt the metabolic response to meet physiological demands. Furthermore, this transmission required the formation of extensive Connexin-43 gap-junction-mediated metabolic networks by arcuate tanycytes. Selectively suppressing either tanycytic monocarboxylate transporters or gap junctions resulted in altered feeding behavior and energy metabolism. Tanycytic intercellular communication and lactate production are thus integral to the mechanism by which hypothalamic neurons that regulate energy and glucose homeostasis efficiently perceive alterations in systemic glucose levels as a function of the physiological state of the organism.

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