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

doi:10.3969/j.issn.1674-8115.2023.12.004

Abstract

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

CLC Number:

R964

SHA Xudong, WANG Chenfei, LU Jia, YU Zhihua. 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.

Figures/Tables 8

Tab 1 Primer sequences used for qRT-PCR （5'→3'）

Oligonucleotide	SOURCE	IDENTIFIER
mouse trpv1 FWD: TGGCTCATATTTGCCTTCAG mouse trpv1 REV: CAGCCCTAGGAGTTGATFGA	Sango Biotech	N/A
mouse ucp2 FWD: GCTGGTGGTTCGGAGAT mouse ucp2 REV: TGAAGTGGCAAGGGAGG	Sango Biotech	N/A
mouse tnf-α FWD: CAGGAGGGAGAACAGAAACTCCA mouse tnf-α REV: CCTGGTTGGCTGCTT	Sango Biotech	N/A
mouse il-1β FWD: GGAGGTGGTGATAGCCGGTAT mouse il-1β REV: TGGGTAATCCATAGAGCCCAG	Sango Biotech	N/A
mouse gapdh FWD: TGATGGCAACAATCTCCAC mouse gapdh REV: CGTCCCGTAGACAAAATGGT	Sango Biotech	N/A

Fig 1 WGCNA in WT and genetic Trpv1 deletion mice before and after high fat feeding

Fig 2 HFD induced liposome switch of brain cells with Trpv1 deficiency

Fig 3 Genetic Trpv1 deletion reduced HFD-induced multiple effects on brain transcriptome

Fig 4 Genetic Trpv1 deletion reduced HFD-induced multiple effects on metabolic pathways of the brain

Fig 5 Genetic Trpv1 deletion ameliorates HFD-induced microglia activation

Fig 6 Up-regulation of TRPV1 in active microglia and reactive astrocytes of HFD mice brains

Fig 7 Genetic Trpv1 deletion attenuate HFD-induced neuroinflammation and mitochondrial activation

TrendMD

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