Lactate activates hypothalamic POMC neurons by intercellular signaling

Abstract 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 fun...

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Autores principales:	P. Órdenes, P. S. Villar, E. Tarifeño-Saldivia, M. Salgado, R. Elizondo-Vega, Ricardo C. Araneda, María A. García-Robles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bec5e3e5f9444ba28e1fdb80c599dc03
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spelling	oai:doaj.org-article:bec5e3e5f9444ba28e1fdb80c599dc032021-11-08T10:48:00ZLactate activates hypothalamic POMC neurons by intercellular signaling10.1038/s41598-021-00947-72045-2322https://doaj.org/article/bec5e3e5f9444ba28e1fdb80c599dc032021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00947-7https://doaj.org/toc/2045-2322Abstract 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.P. ÓrdenesP. S. VillarE. Tarifeño-SaldiviaM. SalgadoR. Elizondo-VegaRicardo C. AranedaMaría A. García-RoblesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q P. Órdenes P. S. Villar E. Tarifeño-Saldivia M. Salgado R. Elizondo-Vega Ricardo C. Araneda María A. García-Robles Lactate activates hypothalamic POMC neurons by intercellular signaling
description	Abstract 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.
format	article
author	P. Órdenes P. S. Villar E. Tarifeño-Saldivia M. Salgado R. Elizondo-Vega Ricardo C. Araneda María A. García-Robles
author_facet	P. Órdenes P. S. Villar E. Tarifeño-Saldivia M. Salgado R. Elizondo-Vega Ricardo C. Araneda María A. García-Robles
author_sort	P. Órdenes
title	Lactate activates hypothalamic POMC neurons by intercellular signaling
title_short	Lactate activates hypothalamic POMC neurons by intercellular signaling
title_full	Lactate activates hypothalamic POMC neurons by intercellular signaling
title_fullStr	Lactate activates hypothalamic POMC neurons by intercellular signaling
title_full_unstemmed	Lactate activates hypothalamic POMC neurons by intercellular signaling
title_sort	lactate activates hypothalamic pomc neurons by intercellular signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bec5e3e5f9444ba28e1fdb80c599dc03
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Lactate activates hypothalamic POMC neurons by intercellular signaling

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