Lactate activates hypothalamic POMC neurons by intercellular signaling.

Autor: Órdenes P; Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Villar PS; Department of Biology Bioscience Research Bldg R-1114, University of Maryland, College Park, MD, 20742, USA., Tarifeño-Saldivia E; Gene Expression and Regulation Laboratory, Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Salgado M; Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Elizondo-Vega R; Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile., Araneda RC; Department of Biology Bioscience Research Bldg R-1114, University of Maryland, College Park, MD, 20742, USA. raraneda@umd.edu., García-Robles MA; Laboratorio de Biología Celular, Departamento de Biología Celular, Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile. mgarcia@udec.cl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Nov 04; Vol. 11 (1), pp. 21644. Date of Electronic Publication: 2021 Nov 04.
DOI: 10.1038/s41598-021-00947-7
Abstrakt: Previous studies indicate that the activity of hypothalamic POMC neurons can be regulated by glucose via intracellular mechanisms, but its regulation by lactate is poorly understood. In addition to its energetic role, lactate acts as a signaling molecule. In this study, we evaluated the function and location of the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1). We used a conditional genetic approach to label POMC neurons and evaluated their sensitivity to lactate using patch-clamp recordings. L-Lactate and 3-chloro-5-hydroxybenzoic acid (3Cl-HBA), HCAR1 specific agonist depolarized POMC neurons and the increase in excitability was abolished by pertussis toxin (PTX), indicating the involvement of Gαi/o-protein-coupled receptors. In addition, the depolarization of a subset of POMC neurons was sensitive to α-cyano-4-hydroxycinnamate (4-CIN), a lactate transporter blocker, suggesting that the depolarization induced by L-lactate can also occur by direct intracellular action. Surprisingly, HCAR1 was not detected in POMC neurons, but instead localized in astrocytes. These results suggest a new lactate-mediated mechanism for astrocyte-neuron intercellular communication.
(© 2021. The Author(s).)
Databáze: MEDLINE
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