Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1

被引：394

作者：

Morland, Cecilie ^{[1
,2
,3
]}

Andersson, Krister A. ^{[1
,2
,3
]}

Haugen, Oyvind P. ^{[1
]}

Hadzic, Alena ^{[1
,2
,3
]}

Kleppa, Liv ^{[1
,3
]}

Gille, Andreas ^{[4
]}

Rinholm, Johanne E. ^{[1
,3
]}

Palibrk, Vuk ^{[5
]}

Diget, Elisabeth H. ^{[1
,6
]}

Kennedy, Lauritz H. ^{[1
,3
]}

Stolen, Tomas ^{[7
]}

Hennestad, Eivind ^{[8
]}

Moldestad, Olve ^{[9
]}

Cai, Yiqing ^{[1
]}

Puchades, Maja ^{[3
]}

Offermanns, Stefan ^{[10
]}

Vervaeke, Koen ^{[8
]}

Bjoras, Magnar ^{[5
]}

Wisloff, Ulrik ^{[7
]}

Storm-Mathisen, Jon ^{[3
]}

Bergersen, Linda H. ^{[1
,3
,6
]}

机构：

[1] Univ Oslo, Dept Oral Biol, Electron Microscopy Lab, Brain & Muscle Energy Grp, NO-0316 Oslo, Norway

[2] Oslo & Akershus Univ Coll, Fac Hlth Sci, Inst Behav Sci, NO-0167 Oslo, Norway

[3] Univ Oslo, Hlth Brain Ageing Ctr, Inst Basic Med Sci, Synapt Neurochem Lab,Div Anat,Dept Mol Med, NO-0317 Oslo, Norway

[4] Heidelberg Univ, Inst Expt & Clin Pharmacol & Toxicol, D-68169 Mannheim, Germany

[5] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, NO-7491 Trondheim, Norway

[6] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, Ctr Hlth Aging, DK-2200 Copenhagen N, Denmark

[7] Norwegian Univ Sci & Technol, Dept Circulat & Med Imaging, KG Jebsen Ctr Exercise Med, NO-7491 Trondheim, Norway

[8] Univ Oslo, Dept Physiol, Lab Neural Computat, NO-0317 Oslo, Norway

[9] Natl Hosp Norway, Oslo Univ Hosp, Ctr Rare Disorders, NO-0424 Oslo, Norway

[10] Max Planck Inst Heart & Lung Res, Dept Pharmacol, D-61231 Bad Nauheim, Germany

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

NEUROGENESIS; EXPRESSION; MODEL; ACID; MICE; RAT; PERICYTES; LIPOLYSIS; HYPOXIA; HEALTH;

D O I：

10.1038/ncomms15557

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 54 条

[1] An Autocrine Lactate Loop Mediates Insulin-Dependent Inhibition of Lipolysis through GPR81 [J].