Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

Nat Commun. 2017 May 23;8:15557. doi: 10.1038/ncomms15557.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Capillaries / cytology
  • Capillaries / drug effects
  • Capillaries / metabolism
  • Injections, Subcutaneous
  • Lactic Acid / administration & dosage
  • Lactic Acid / blood
  • Lactic Acid / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Models, Animal
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Neovascularization, Physiologic / physiology*
  • Pericytes / metabolism
  • Physical Conditioning, Animal / physiology*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Hcar1 protein, mouse
  • Receptors, G-Protein-Coupled
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Lactic Acid