Lauric Acid Alleviates Neuroinflammatory Responses by Activated Microglia: Involvement of the GPR40-Dependent Pathway

Yasunori Nishimura, Mitsuaki Moriyama, Kenji Kawabe, Hideyo Satoh, Katsura Takano, Yasu Taka Azuma, Yoichi Nakamura

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In several neurodegenerative diseases such as Alzheimer’s disease (AD), microglia are hyperactivated and release nitric oxide (NO) and proinflammatory cytokines, resulting its neuropathology. Mounting evidence indicates that dietary supplementation with coconut oil (CNO) reduces the cognitive deficits associated with AD; however, the precise mechanism(s) underlying the beneficial effect of CNO are unknown. In the present study, we examined the effects of lauric acid (LA), a major constituent of CNO, on microglia activated experimentally by lipopolysaccharide (LPS), using primary cultured rat microglia and the mouse microglial cell line, BV-2. LA attenuated LPS-stimulated NO production and the expression of inducible NO synthase protein without affecting cell viability. In addition, LA suppressed LPS-induced reactive oxygen species and proinflammatory cytokine production, as well as phosphorylation of p38-mitogen activated protein kinase and c-Jun N-terminal kinase. LA-induced suppression of NO production was partially but significantly reversed in the presence of GW1100, an antagonist of G protein-coupled receptor (GPR) 40, which is an LA receptor on the plasma membrane. LA also decreased LPS-induced phagocytosis, which was completely reversed by co-treatment with GW1100. Moreover, LA alleviated amyloid-β-induced enhancement of phagocytosis. These results suggest that attenuation of microglial activation by LA may occur via the GPR40-dependent pathway. Such effects of LA may reduce glial activation and the subsequent neuronal damage in AD patients who consume CNO.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalNeurochemical Research
DOIs
Publication statusAccepted/In press - Jun 26 2018

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Keywords

  • Coconut oil
  • GPR40
  • Lauric acid
  • Microglia
  • Neuroinflammation
  • Phagocytosis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Nishimura, Y., Moriyama, M., Kawabe, K., Satoh, H., Takano, K., Azuma, Y. T., & Nakamura, Y. (Accepted/In press). Lauric Acid Alleviates Neuroinflammatory Responses by Activated Microglia: Involvement of the GPR40-Dependent Pathway. Neurochemical Research, 1-13. https://doi.org/10.1007/s11064-018-2587-7