Regulation of high-fat diet-induced microglial metabolism by transient receptor potential vanilloid type 1
10.3969/j.issn.1674-8115.2023.12.004
- VernacularTitle:瞬时受体电位香草素1型对高脂饮食诱导的小胶质细胞代谢的调控
- Author:
Xudong SHA
1
;
Chenfei WANG
;
Jia LU
;
Zhihua YU
Author Information
1. 上海交通大学医学院药理学与化学生物学系,上海 200032
- Keywords:
transient receptor potential vanilloid type 1(TRPV1);
microglia;
metabolism;
lipid;
mitochondria
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2023;43(12):1493-1506
- CountryChina
- Language:Chinese
-
Abstract:
Objective·Transcriptomic and lipidomic analysis techniques were used to investigate the role of transient receptor potential vanilloid type 1(TRPV1)channel activation in the regulation of high-fat diet-induced microglial metabolism.Methods· Eight-week-old C57BL/6J mice(WT)and Trpvl-/-(KO)mice were used as experimental animals,and fed high-fat diet(HFD)for 3 days,7 days,and 8 weeks to induce modelling(WT and KO groups,n=3;WT-HFD and KO-HFD groups,n=4).TRPV1 channel expression and cellular localisation were measured by immunofluorescence in the brains of mice in the WT-HFD and KO-HFD group.RNA sequencing and liquid chromatography-mass spectrometry were performed to determine the brain phenotype of mice in the WT-HFD and KO-HFD groups.Results·The expression level of Trpvl mRNA in microglia was significantly increased in mice in the WT-HFD group compared to mice in the WT group.The expression levels of genes related to brain lipid metabolism,mitochondrial function,glucose transfer,and glycolysis were down-regulated in the KO-HFD group of mice compared with the WT-HFD group of mice.Lipidomic analysis showed that although lipids accumulated in the brain tissue of mice in the KO-HFD group,Trpv1 knockdown attenuated HFD-induced microglia activation,and in addition the TRPV1 agonist capsaicin attenuated palmitate-induced depolarisation of mitochondrial membrane potential in vitro.Conclusion·Together,these findings suggest that TRPV1 regulates lipid and glucose metabolism in microglia via fuel availability driven by a mitochondrial mechanism.
