Dataset Information

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD₂-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

ABSTRACT:

Background

Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D₂ (PGD₂) production and PGD₂-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120 (free fatty acid receptor 4), which is expressed in intestine, could be activated by polyunsaturated fatty acids (PUFA), thereby mediating secretion of glucagon-like peptide-1 (GLP-1). Dysfunction of GPR120 results in obesity in both mice and humans.

Methods

To reveal the relationship between PGD₂-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function with gene and protein expression, histological, and behavioral analysis in GPR120 knockout (KO) mice.

Results

In the current study, we discovered notable neuroinflammation (increased PGD₂ production and microglial activation) and neurodegeneration (declines in neurogenesis, hippocampal volume, and cognitive function) in GPR120 KO mice. We also found that Hematopoietic-prostaglandin D synthase (H-PGDS) was expressed in microglia, microglia were activated by PGD₂, H-PGDS expression was upregulated in GPR120 KO hippocampus, and inhibition of PGD₂ production attenuated this neuroinflammation. GPR120 KO mice exhibited reduced intestinal, plasma, and intracerebral GLP-1 contents. Peripheral administration of a GLP-1 analogue, liraglutide, reduced PGD₂-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice.

Conclusions

Our results suggest that neurological phenotypes in GPR120 KO mice are probably caused by dysfunction of intestinal GPR120. These observations raise the possibility that intestinal GLP-1 secretion, stimulated by intestinal GPR120, may remotely contributed to suppress PGD₂-microglia-provoked neuroinflammation in the hippocampus.

SUBMITTER: Iwasa K

PROVIDER: S-EPMC8711188 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD<sub>2</sub>-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

Iwasa Kensuke K Yamamoto Shinji S Yamashina Kota K Yagishita-Kyo Nan N Maruyama Kei K Awaji Takeo T Takei Yoshinori Y Hirasawa Akira A Yoshikawa Keisuke K

Journal of neuroinflammation 20211227 1

<h4>Background</h4>Neuroinflammation is a key pathological component of neurodegenerative disease and is characterized by microglial activation and the secretion of proinflammatory mediators. We previously reported that a surge in prostaglandin D<sub>2</sub> (PGD<sub>2</sub>) production and PGD<sub>2</sub>-induced microglial activation could provoke neuroinflammation. We also reported that a lipid sensor GPR120 (free fatty acid receptor 4), which is expressed in intestine, could be activated by ...[more]

PMID: 34961526

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Dataset Information

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD₂-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

Background

Methods

Results

Conclusions

Publications

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD<sub>2</sub>-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD2-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

Background

Methods

Results

Conclusions

Publications

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD<sub>2</sub>-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A peripheral lipid sensor GPR120 remotely contributes to suppression of PGD₂-microglia-provoked neuroinflammation and neurodegeneration in the mouse hippocampus.