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Med Sci Sports Exerc. 2020 Feb 19. doi: 10.1249/MSS.0000000000002310. [Epub ahead of print]

Exercise Induces Different Molecular Responses in Trained and Untrained Human Muscle.

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Åstrand Laboratory, Swedish School of Sport and Health Sciences, Stockholm, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, School of Medicine, Stanford University, Stanford, CA.
Department of Learning, Informatics, Management, and Ethics, Karolinska Institutet, Stockholm, Sweden.



Human skeletal muscle is thought to have heightened sensitivity to exercise stimulus when it has been previously trained (i.e., it possesses "muscle memory"). We investigated whether basal and acute resistance exercise-induced gene expression and cell signaling events are influenced by previous strength training history.


Accordingly, 19 training naïve women and men completed 10 weeks of unilateral leg strength training, followed by 20 weeks of detraining. Subsequently, an acute resistance exercise session was performed for both legs, with vastus lateralis biopsies taken at rest and 1 h after exercise in both legs (memory and control).


The phosphorylation of AMPK and eEF2 was higher in the memory leg than in the control leg at both time points. Post-exercise phosphorylation of 4E-BP1 was higher in the memory leg than in the control leg. The memory leg had lower basal mRNA levels of total PGC1α, and, unlike the control leg, exhibited increases in PGC1α-ex1a transcripts after exercise. In the genes related to myogenesis (SETD3, MYOD1, and MYOG), mRNA levels differed between the memory and the untrained leg; these effects were evident primarily in the male subjects. Expression of the novel gene SPRYD7 was lower in the memory leg at rest and decreased after exercise only in the control leg, but SPRYD7 protein levels were higher in the memory leg.


In conclusion, several key regulatory genes and proteins involved in muscular adaptations to resistance exercise are influenced by previous training history. Although the relevance and mechanistic explanation for these findings need further investigation, they support the view of a molecular muscle memory in response to training.

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