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Lactate administration reproduces specific brain and liver exercise‐related changes
Author(s) -
E Lezi,
Lu Jianghua,
Selfridge J. Eva,
Burns Jeffrey M.,
Swerdlow Russell H.
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12394
Subject(s) - medicine , endocrinology , gluconeogenesis , activator (genetics) , receptor , lactate threshold , gene expression , peroxisome proliferator activated receptor , physical exercise , biology , alpha (finance) , treadmill , metabolism , blood lactate , gene , biochemistry , heart rate , construct validity , nursing , blood pressure , patient satisfaction
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.In mice, exercise induces liver peroxisome proliferator‐activated receptor gamma co‐activator 1 alpha (PGC‐1α) mRNA, increases gluconeogenesis, but otherwise minimally affects respiration infrastructure. Brain PGC‐1‐related co‐activator (PRC) mRNA, mitochondrial DNA (mtDNA), and vascular endothelial growth factor A (VEGF‐A) mRNA increase, whereas tumor necrosis factor alpha (TNF‐α) mRNA decreases. Lactate injection reproduces some, but not all, of these effects. Exercise‐generated lactate, therefore, likely mediates some exercise‐associated liver and brain effects.