Lactate administration reproduces specific brain and liver exercise-related changes. J Neurochem 2013 Oct;127(1):91-100
Date
08/10/2013Pubmed ID
23927032Pubmed Central ID
PMC4276250DOI
10.1111/jnc.12394Scopus ID
2-s2.0-84884896415 (requires institutional sign-in at Scopus site) 73 CitationsAbstract
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.
Author List
E L, Lu J, Selfridge JE, Burns JM, Swerdlow RHAuthor
Lezi E PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlood Glucose
Body Weight
Brain
Brain Chemistry
DNA, Mitochondrial
Energy Metabolism
Gene Dosage
Immunohistochemistry
Insulin
Lactic Acid
Liver
Male
Mice
Mice, Inbred C57BL
Nuclear Respiratory Factor 1
Physical Conditioning, Animal
Polymerase Chain Reaction
Transcription Factors
Vascular Endothelial Growth Factor A