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, which is expressed in intestine, could be activated by polyunsaturated fatty acids, thereby mediating secretion of glucagon-like peptide-1 (GLP-1). To reveal the relationship between PGD₂-microglia-provoked neuroinflammation and intestinal PUFA/GPR120 signaling, we investigated neuroinflammation and neuronal function in GPR120 knockout (KO) mice.
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 inhibition of PGD₂ production and potentiation of GLP-1 bioactivity reduced PGD₂-microglia-provoked neuroinflammation and further neurodegeneration in GPR120 KO mice.
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.