Lactate administration reproduces specific brain and liver exercise-related changes.
The effects of exercise are not limited to muscle, and its ability to mitigate some chronic diseases is under study. A more complete understanding of how exercise impacts non-muscle tissues might facilitate design of clinical trials and exercise mimetics. Here, we focused on lactate's ability to mediate changes in liver and brain bioenergetic-associated parameters. In one group of experiments, C57BL/6 mice underwent 7 weeks of treadmill exercise sessions at intensities intended to exceed the lactate threshold. Over time, the mice dramatically increased their lactate threshold. To ensure that plasma lactate accumulated during the final week, the mice were run to exhaustion. In the liver, mRNA levels of gluconeogenesis-promoting genes increased. While peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) expression increased, there was a decrease in PGC-1β expression, and overall gene expression changes favored respiratory chain down-regulation. In the brain, PGC-1α and PGC-1β were unchanged, but PGC-1-related co-activator expression and mitochondrial DNA copy number increased. Brain tumor necrosis factor alpha expression fell, whereas vascular endothelial growth factor A expression rose. In another group of experiments, exogenously administered lactate was found to reproduce some but not all of these observed liver and brain changes. Our data suggest that lactate, an exercise byproduct, could mediate some of the effects exercise has on the liver and the brain, and that lactate itself can act as a partial exercise mimetic.
University of Kansas Alzheimer's Disease Center, Kansas City, Kansas, USA; Department of Physical Therapy and Rehabilitation Science, University of Kansas Medical Center, Kansas City, Kansas, USA.
Lezi
L
E
Jianghua
J
Lu
J Eva
JE
Selfridge
Jeffrey M
JM
Burns
Russell H
RH
Swerdlow
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D018628:Gene Dosage; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D001786:Blood Glucose; D004272:DNA, Mitochondrial; D007328:Insulin; D051266:Nuclear Respiratory Factor 1; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D019344:Lactic Acid
brain; exercise; lactate; liver