Ø Neuroinflammation through Microglia Odorant Receptor
Microglia, the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We found that Microglia express high levels of two mouse odorant receptors (ORs), Olfr110 and Olfr111, which recognize a pathogenic metabolite, secreted by pathogen (Lee et al. 2020). Greater knowledge of these interactions could provide fundamental insight into the physiological and pathological roles of ectopically expressed ORs in brain. This interaction induces microglial activation, suggesting a unique pathogen-derived metabolite-mediated Pathogen–Brain Axisassociated with neuroinflammation. Conventional pattern recognition receptors involved in microglial activation are receptors for pathogen-derived macromolecules, including cell wall components, peptidoglycan, lipoteichoic acid, and flagellin. Our findings provide an alternative strategy for pathogen recognition by microglia that involves small metabolite–OR interactions.
How to cite:
Click Lee N, Jae Y, Kim M, Cho T, Lee C, Hong YR, Hyeon DY, Ahn S, Kwon H, Kim K, Jung JH, Chae S, Shin JO, Bok J, Byun Y, Hwang D, Koo J. A pathogen-derived metabolite induces microglial activation via odorant receptors. FEBS J. 2020 Jan 30. doi: 10.1111/febs.15234.
Ø Brain Energy Metabolism through Astrocyte Odorant Receptor
Astrocytes are the most abundant cell type in the brain and they are involved in Brain Energy Metabolism through astrocyte-neuron metabolic cooperation. 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. Stimulation with MCFAs increases glycolytic activity and consequently induces release of lactate by astrocytes into the extracellular space. However, little is known about the molecular mechanism by which astrocytes sense free FAs and increase lactate release, and by which GPCRs recognize free FAs in astrocytes. We demonstrate a novel molecular mechanism by which astrocytes recognize free MCFAs (Lee et al. 2018). Our findings suggest that astrocytes play crucial roles in lipid sensing in the brain and modulate metabolism in nearby neurons by releasing lactate and/or GABA. We propose that modulation of lactate and GABA production mediated by a GPCR and MAO-B is a new approach to control energy metabolism in astrocytes.
How to cite:
Click Lee N, Sa M, Hong YR, Lee CJ, Koo J. Fatty Acid Increases cAMP-dependent Lactate and MAO-B-dependent GABA Production in Mouse Astrocytes by Activating a Gαs Protein-coupled Receptor. Exp Neurobiol. 2018 Oct;27(5):365-376. doi: 10.5607/en.2018.27.5.365.
Ø Metabolism through Pancreatic Odorant Receptor