Abstract
Context: Endurance-trained athletes have high oxidative capacities, enhanced insulin sensitivities, and high intracellular lipid accumulation in muscle. These characteristics are likely due to altered gene expression levels in muscle. Design and setting: We compared intramyocellular lipid (IMCL), insulin sensitivity, and gene expression levels of the muscle in eight nonobese healthy men (control group) and seven male endurance athletes (athlete group). Their IMCL levels were measured by proton-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by glucose infusion rate (GIR) during a euglycemic–hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR (qRT-PCR) and microarray analysis. Results: IMCL levels in the tibialis anterior muscle were approximately 2.5 times higher in the athlete group compared to the control group, while the IMCL levels in the soleus muscle and GIR were comparable. In the microarray hierarchical clustering analysis, gene expression patterns were not clearly divided into control and athlete groups. In a gene set enrichment analysis with Gene Ontology gene sets, “RESPONSE TO LIPID” was significantly upregulated in the athlete group compared with the control group. Indeed, qRT-PCR analysis revealed that, compared to the control group, the athlete group had 2–3 times higher expressions of proliferator-activated receptor gamma coactivator-1 alpha (PGC1A), adiponectin receptors (AdipoRs), and fatty acid transporters including fatty acid transporter-1, plasma membrane-associated fatty acid binding protein, and lipoprotein lipase. Conclusions: Endurance runners with higher IMCL levels have higher expression levels of genes related to lipid metabolism such as PGC1A, AdipoRs, and fatty acid transporters in muscle.
Highlights
Skeletal muscle has been shown to adapt to various stimuli, including exercise
intramyocellular lipid (IMCL) levels in tibialis anterior muscle (TA) were approximately 2.5 times higher in the athlete group compared with the control group, while IMCL levels in soleus muscle (SOL) and glucose infusion rate (GIR) were comparable between the groups
The quantitative RT-PCR (qRT-PCR) analysis revealed that the athlete group had expression levels of several genes related to fatty acid transportation, including fatty acid transporter 1 (FATP1), FABPpm, and lipoprotein lipase (LPL), that were approximately 2 times higher than in the control group
Summary
Skeletal muscle has been shown to adapt to various stimuli, including exercise. endurance training enhances mitochondrial biogenesis, lipid and glucose transport, lipid oxidation, and oxidative capacity in muscle [1,2,3,4,5,6,7]. Endurance-trained athletes who have high oxidative capacity and enhanced insulin sensitivity have higher intramyocellular (IMCL) content [8,9]. These characteristics of the muscles in endurance-trained athletes are likely acquired as a long-term effect of training. Several studies have compared global gene expression levels in skeletal muscle using microarrays before and after endurance training for 6 to 20 weeks [10,11,12,13]. Stepto et al [14] demonstrated that cyclists with long-term (> 5 years) endurance training have higher expressions of gene clusters related to mitochondrial/oxidative capacity than the control subjects. We performed quantitative RT-PCR (qRT-PCR) to measure gene expression levels related to IMCL accumulation and insulin sensitivity, which were clarified in our previous study [16]
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