Journal of Shanghai Jiao Tong University (Medical Science) >

2023 , Vol. 43 >Issue 12: 1493 - 1506

DOI: https://doi.org/10.3969/j.issn.1674-8115.2023.12.004

Basic research

Regulation of high-fat diet-induced microglial metabolism by transient receptor potential vanilloid type 1

  • Xudong SHA ,
  • Chenfei WANG ,
  • Jia LU ,
  • Zhihua YU
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  • Department of Pharmacology and Chemical Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
YU Zhihua, E-mail: yuzhihua@shsmu.edu.cn.

Received date: 2023-04-17

  Accepted date: 2023-11-09

  Online published: 2024-02-01

Supported by

National Natural Science Foundation of China(82173791);Shanghai Science and Technology Commission Fund Grant(23ZR1436600)

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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 Trpv1-/- (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 Trpv1 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.

Key words： transient receptor potential vanilloid type 1(TRPV1); microglia; metabolism; lipid; mitochondria

Cite this article

Xudong SHA , Chenfei WANG , Jia LU , Zhihua YU . Regulation of high-fat diet-induced microglial metabolism by transient receptor potential vanilloid type 1[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023 , 43(12) : 1493 -1506 . DOI: 10.3969/j.issn.1674-8115.2023.12.004

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