Endothelium-derived lactate is required for pericyte function and blood-brain barrier maintenance

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.

Automated summary

Endothelial cells rely on glycolysis for energy production, resulting in lactate production. Pericytes uptake endothelium-derived lactate and use it for energy generation and amino acid biosynthesis. The proximity between endothelial cells and pericytes is crucial for the transport of lactate. Inhibition of endothelial lactate production leads to blood-brain barrier breakdown, while lactate administration can restore these abnormalities to some extent.