4.6 Article

Depletion of microglia mitigates cerebrovascular dysfunction in diet-induced obesity mice

Journal

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.00086.2021

Keywords

cerebrovascular dysfunction; IL-18; microglia; neuroinflammation; obesity

Funding

  1. National Natural Science Foundation of China [91539125, 81573146]

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This study demonstrates the important role of neuroinflammation involving microglia in obesity-related cerebrovascular dysfunction, with PLX3397 treatment improving brain artery function in mice, and excessive IL-18 leading to vascular dysfunction in the mouse brain.
Obesity is frequently associated with cerebrovascular dysfunction; however, the underlying mechanism remains less well understood. In this study, by using pharmacological approaches, we show that neuroinflammation involving microglia plays an important role in obesity-related cerebrovascular dysfunction. PLX3397 treatment, which leads to depletion of microglia, reduced the wall thickness and collagen deposition in the basilar artery of diet-induced obesity (DIO) mice. Besides, the phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 was enhanced, suggesting improved endothelial function of the basilar artery. The wire myography data show that acetylcholine-elicited relaxation of basilar artery isolated from DIO mice was improved after the treatment with PLX3397. Moreover, our data demonstrate that brain administration of IL-18 impaired cerebrovascular function in mice with normal body weight. Together, these data suggest that neuroinflammation involving microglia is important in obesity-related vascular dysfunction in the brain. NEW & NOTEWORTHY We reported that microglia, the resident immune cells in the brain, contribute to obesity-related cerebrovascular dysfunction in mice. Moreover, we showed that excessive IL-18 can lead to vascular dysfunction in mouse brain.

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