Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

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Documents

  • Cecilie Morland
  • Krister A. Andersson
  • Oyvind P. Haugen
  • Alena Hadzic
  • Liv Kleppa
  • Andreas Gille
  • Johanne E. Rinholm
  • Vuk Palibrk
  • Elisabeth H. Diget
  • Lauritz H. Kennedy
  • Tomas Stolen
  • Eivind Hennestad
  • Olve Moldestad
  • Yiqing Cai
  • Maja Puchades
  • Stefan Offermanns
  • Koen Vervaeke
  • Magnar Bjoras
  • Ulrik Wisloff
  • Jon Storm-Mathisen
Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise, increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.
Original languageEnglish
Article number15557
JournalNature Communications
Volume8
Number of pages9
ISSN2041-1723
DOIs
Publication statusPublished - 2017

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