Endothelial cells differ from other cell types responsible for the formation of the vascular wall in their unusual reliance on glycolysis for most energy needs, which results in extensive production of lactate. We find that endothelium-derived lactate is taken up by pericytes, and contributes substantially to pericyte metabolism including energy generation and amino acid biosynthesis. Endothelial-pericyte proximity is required to facilitate the transport of endothelium-derived lactate into pericytes. Inhibition of lactate production in the endothelium by deletion of the glucose transporter-1 (GLUT1) in mice results in loss of pericyte coverage in the retina and brain vasculatures, leading to the blood-brain barrier breakdown and increased permeability. These abnormalities can be largely restored by oral lactate administration. Our studies demonstrate an unexpected link between endothelial and pericyte metabolisms and the role of endothelial lactate production in the maintenance of the blood-brain barrier integrity. In addition, our observations indicate that lactate supplementation could be a useful therapeutic approach for GLUT1 deficiency metabolic syndrome patients.

中文翻译：

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内皮衍生的乳酸是周细胞功能和血脑屏障维持所必需的。

内皮细胞与负责血管壁形成的其他细胞类型不同，它们异常依赖糖酵解来满足大多数能量需求，从而导致乳酸的大量产生。我们发现内皮衍生的乳酸被周细胞吸收，并显着促进周细胞代谢，包括能量产生和氨基酸生物合成。需要内皮-周细胞接近以促进内皮衍生的乳酸转运到周细胞中。通过删除小鼠中的葡萄糖转运蛋白 1 (GLUT1) 抑制内皮细胞中的乳酸生成，导致视网膜和脑血管系统中周细胞覆盖的丧失，导致血脑屏障破裂和通透性增加。这些异常可以通过口服乳酸盐在很大程度上得到恢复。我们的研究表明，内皮和周细胞代谢与内皮乳酸生成在维持血脑屏障完整性中的作用之间存在意想不到的联系。此外，我们的观察表明补充乳酸可能是 GLUT1 缺乏代谢综合征患者的一种有用的治疗方法。