Early Muscle Gene Expression Changes With Eccentric Exercise Uniquely Associated With Peak Strength Loss

Abstract

PURPOSE: Novel eccentric (ECC) exercise typically leads to strength loss that persists for several days after exercise, which varies widely between subjects. The mechanisms responsible for this variation are poorly understood. Here, we identified biological processes related to the extent of peak strength loss via global gene expression profiling. METHODS: In a previously published study, vastus lateralis biopsies were collected from 35 young men 3hr post-ECC exercise (100 maximal voluntary eccentric (ECC) actions on isokinetic dynamometer, non-exercised contralateral leg (CON) as a control). Maximal isometric strength of the knee extensors was assessed on a Biodex dynamometer. RNA isolated using the TRIzol method was used to generate global gene expression profiles on the Agilent Whole Genome Microarray platform. The current study is a retrospective analysis of the relationship between gene expression changes and peak strength loss from that previous study (GSE23697). Partek Genomics Suite correlated peak strength loss post-ECC (0-5d) with gene expression in ECC relative to intra-subject paired CON. Correlated genes (p<0.05) were analyzed using Ingenuity Pathway Analysis. RESULTS: Peak strength loss averaged 50.7±20.1% with a range of 9.7% to 96.0%. Pearson linear correlation detected 2333 genes (p<0.05) relating ECC (relative to CON) to peak strength loss, where 2201 and 132 genes were positively and negatively correlated to peak strength loss, respectively. Pathway analysis found 37 canonical pathways (p<0.05) associated with peak strength loss, including: glutamate receptor signaling (14 genes; -log p-value=3.22), serotonin receptor signaling (9 genes; -log p-value=2.22), GABA receptor signaling (18 genes; -log p-value=1.78), and cAMP mediated signaling (27 genes; -log p-value=1.58). CONCLUSION: In a model of moderate exercise-induced muscle damage, we assessed early changes in muscle gene expression and related these changes to variation in peak strength loss. Biological pathways that relate to the extent of muscle dysfunction include several neurotransmitter pathways, as well as cell signaling pathways such as cAMP. Insight into early drivers of strength loss could identify targets to reduce muscle dysfunction and optimize recovery in those prone to dysfunction following exercise.