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Original Article

Exp Neurobiol 2018; 27(5): 365-376

Published online October 31, 2018

© The Korean Society for Brain and Neural Sciences

Fatty Acid Increases cAMP-dependent Lactate and MAO-B-dependent GABA Production in Mouse Astrocytes by Activating a Gαs Protein-coupled Receptor

NaHye Lee1,2,3,†, Moonsun Sa4,5,6,†, Yu Ri Hong2, C. Justin Lee4,5,6*, and JaeHyung Koo2,3*

1Department of Brain and Cognitive Sciences, DGIST, Daegu 42988, Korea.

2Department of New Biology, DGIST, Daegu 42988, Korea.

3Center for Bio-Convergence Spin System, DGIST, Daegu 42988, Korea.

4KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.

5Center for Neuroscience and Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

6Center for Glia-Neuron Interaction, KIST, Seoul 02792, Korea.

Correspondence to: *To whom correspondence should be addressed.
JaeHyung Koo, TEL: 82-53-785-6112, FAX: 82-53-785-1819
C. Justin Lee, TEL: 82-2-958-6940, FAX: 82-2-958-6919
These authors contributed equally to this work.

Received: October 2, 2018; Revised: October 20, 2018; Accepted: October 24, 2018

Medium-chain fatty acids (MCFAs) are mostly generated from dietary triglycerides and can penetrate the blood-brain barrier. Astrocytes in the brain use MCFAs as an alternative energy source. In addition, MCFAs have various regulatory and signaling functions in astrocytes. However, it is unclear how astrocytes sense and take up MCFAs. This study demonstrates that decanoic acid (DA; C10), a saturated MCFA and a ligand of Gαs protein-coupled receptors (Gαs-GPCRs), is a signaling molecule in energy metabolism in primary astrocytes. cAMP synthesis and lactate release were increased via a putative Gαs-GPCR and transmembrane adenylyl cyclase upon short-term treatment with DA. By contrast, monoamine oxidase B-dependent gamma-aminobutyric acid (GABA) synthesis was increased in primary cortical and hypothalamic astrocytes upon long-term treatment with DA. Thus, astrocytes respond to DA by synthesizing cAMP and releasing lactate upon short-term treatment, and by synthesizing and releasing GABA upon long-term treatment, similar to reactive astrocytes. Our data suggest that astrocytes in the brain play crucial roles in lipid-sensing via GPCRs and modulate neuronal metabolism or activity by releasing lactate via astrocyte-neuron lactate shuttle or GABA to influence neighboring neurons.

Graphical Abstract

Keywords: astrocytes, medium-chain fatty acids, cAMP, lactate, decanoic acid, gamma-aminobutyric acid