Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO2max

Abstract

The relationship between inborn maximal oxygen uptake (VO(2max)) and skeletal muscle gene expression is unknown. Since low VO(2max) is a strong predictor of cardiovascular mortality, genes related to low VO(2max) might also be involved in cardiovascular disease. To establish the relationship between inborn VO(2max) and gene expression, we performed microarray analysis of the soleus muscle of rats artificially selected for high- and low running capacity (HCR and LCR, respectively). In LCR, a low VO(2max) was accompanied by aggregation of cardiovascular risk factors similar to the metabolic syndrome. Although sedentary HCR were able to maintain a 120% higher running speed at VO(2max) than sedentary LCR, only three transcripts were differentially expressed (FDR <or=0.05) between the groups. Sedentary LCR expressed high levels of a transcript with strong homology to human leucyl-transfer RNA synthetase, of whose overexpression has been associated with a mutation linked to mitochondrial dysfunction. Moreover, we studied exercise-induced alterations in soleus gene expression, since accumulating evidence indicates that long-term endurance training has beneficial effects on the metabolic syndrome. In terms of gene expression, the response to exercise training was more pronounced in HCR than LCR. HCR upregulated several genes associated with lipid metabolism and fatty acid elongation, whereas LCR upregulated only one transcript after exercise training. The results indicate only minor differences in soleus muscle gene expression between sedentary HCR and LCR. However, the inborn level of fitness seems to influence the transcriptional adaption to exercise, as more genes were upregulated after exercise training in HCR than LCR.

Fig. 1.

Running speed (m/s) at maximal oxygen uptake (VO_2max) before and after the exercise period. LCR-S, sedentary low capacity runners; HCR-S, sedentary high capacity runners; LCR-T, exercise-trained low capacity runners; HCR-T, exercise-trained high capacity runners.

Fig. 2.

Staining of myosin fast fibers in soleus muscle cross sections. An example of myosin fast staining (dark fields) of a sedentary HCR is included. LCR, low capacity runners; HCR, high capacity runners; NS, not significant.

Fig. 3.

Heat map of the most significant transcripts. Transcripts with a high expression are shown in red and transcripts with a low expression are shown in yellow.

Fig. 4.

Protein levels of insulin-like growth factor 1 (IGF1, A) and leucyl-transfer RNA synthetase 2 (LARS2, B) in all the 4 groups (n = 4 in each group).