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The impact of endurance exercise on global and AMPK gene-specific DNA methylation

: King-Himmelreich, T.S.; Schramm, S.; Wolters, M.C.; Schmetzer, J.; Möser, C.V.; Knothe, C.; Resch, E.; Peil, J.; Geisslinger, G.; Niederberger, E.


Biochemical and biophysical research communications 474 (2016), No.2, pp.284-290
ISSN: 0006-291X
Deutsche Forschungsgemeinschaft DFG
Journal Article
Fraunhofer IME ()

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPK alpha 2 gene. These regulations were associated with a reduced AMPK alpha 2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPK alpha 2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPK alpha 2 gene expression.