Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status

Abstract

Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H(+) and lactate anion exchange during physical activity.

<b>Cellular distributions of monocarboxylate transporters: a r</b><b>eview </b>

“…The production of lactate by one tissue and use by another is representative of the lactate shuttle: the mosaic distribution pattern of oxidative and glycolytic fibers is favorable for the exchange of lactate. Exercise may produce greater increases in MCT1 than MCT4 expression (148). On the other hand, denervation for 3 weeks brings about a significant decrease in the expression of MCT4 as well as MCT1 (158).…”

Tissue-Specific Expression of Monocarboxylate Transporters during Fasting in Mice

“…noradrenaline, insulin, IGF-1, butyrate or by other regulatory factors like exercise, hypoxia or the diabetic state. These modulations were shown to be linked to regulatory proteins like NF-κB, calcineurin, AMPK, PGC1α, HIF-1α and mTOR [22]–[28]. The regulation of the thyroid hormone transporters MCT8 and MCT10 remains virtually unknown [29].…”

McArdle Disease and Exercise Physiology

“…For example, 14 weeks of moderate aerobic exercise training (cycling for 30–40 minutes at an intensity corresponding to 60%–70% of maximal heart rate, 4 times per week) increased the peak cardiac output of MD patients by 15% and the activity of mitochondrial enzymes, citrate synthase and hydroxyacyl CoA dehydrogenase, by 60%–80% [43]. In healthy subjects, it is well known that exercise training increases the expression of glucose [44,45], lactate [46,47], and fatty acid transporters [48,49] in muscle; in contrast, physical inactivity decreases the expression of these substrate transporters [50,51,52]. Although the effects of exercise training on metabolite transporters in MD patients have not yet been investigated, these data suggest that the capacity for delivery and oxidation of blood-borne fuels increases with exercise training in MD patients.…”