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Neurochemical Research

, Volume 43, Issue 9, pp 1723–1735 | Cite as

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
Original Paper

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.

Keywords

Microglia Lauric acid Coconut oil Neuroinflammation GPR40 Phagocytosis 

Abbreviations

Amyloid-beta

AD

Alzheimer’s disease

βHB

β-Hydroxybutyrate

BBB

Blood–brain barrier

CNO

Coconut oil

CNS

Central nervous system

DMEM

Dulbecco’s modified Eagle medium

ERK

Extracellular signal-regulated kinase

FBS

Fetal bovine serum

GPR

G protein-coupled receptor

H2DCFDA

2′,7′-dichlorodihydrofluorescein diacetate

IL

Interleukin

iNOS

Inducible nitric oxide synthase

JNK

c-Jun N-terminal kinase

KB

Ketone body

LA

Lauric acid

LPS

Lipopolysaccharide

MAPK

Mitogen activated protein kinase

MCFAs

Medium-chain fatty acids

MCTs

Medium-chain triglycerides

MTT

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide

NO

Nitric oxide

NOX

NADPH oxidase

PD

Parkinson’s disease

ROS

Reactive oxygen species

TLRs

Toll-like receptors

TNFα

Tumor necrosis factor-α

Notes

Acknowledgements

This work was supported in part by JSPS KAKENHI Grant Numbers 17K08127 (to M.M.), 15K07768 (to Y.Na.), and 17K15390 (to K.T.).

Compliance with Ethical Standards

Conflict of interest

All authors in this paper declare that there are no conflicts of interest in this research.

Supplementary material

11064_2018_2587_MOESM1_ESM.pptx (59 kb)
Supplementary material 1 (PPTX 58 KB)

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Authors and Affiliations

  1. 1.Laboratory of Integrative Physiology in Veterinary SciencesOsaka Prefecture UniversityIzumisanoJapan
  2. 2.Department of Regenerative ScienceOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  3. 3.Laboratory of Veterinary PharmacologyOsaka Prefecture UniversityIzumisanoJapan

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