Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
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Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1. / Morland, Cecilie; Andersson, Krister A.; Haugen, Oyvind P.; Hadzic, Alena; Kleppa, Liv; Gille, Andreas; Rinholm, Johanne E.; Palibrk, Vuk; Diget, Elisabeth H.; Kennedy, Lauritz H.; Stolen, Tomas; Hennestad, Eivind; Moldestad, Olve; Cai, Yiqing; Puchades, Maja; Offermanns, Stefan; Vervaeke, Koen; Bjoras, Magnar; Wisloff, Ulrik; Storm-Mathisen, Jon; Bergersen, Linda H.
In: Nature Communications, Vol. 8, 15557, 2017.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1
AU - Morland, Cecilie
AU - Andersson, Krister A.
AU - Haugen, Oyvind P.
AU - Hadzic, Alena
AU - Kleppa, Liv
AU - Gille, Andreas
AU - Rinholm, Johanne E.
AU - Palibrk, Vuk
AU - Diget, Elisabeth H.
AU - Kennedy, Lauritz H.
AU - Stolen, Tomas
AU - Hennestad, Eivind
AU - Moldestad, Olve
AU - Cai, Yiqing
AU - Puchades, Maja
AU - Offermanns, Stefan
AU - Vervaeke, Koen
AU - Bjoras, Magnar
AU - Wisloff, Ulrik
AU - Storm-Mathisen, Jon
AU - Bergersen, Linda H.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1038/ncomms15557
DO - 10.1038/ncomms15557
M3 - Journal article
C2 - 28534495
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 15557
ER -
ID: 182542082