Lactate is not only the end product of glycolysis but also an oxidizable substrate in skeletal muscles.1,2 Lactate is primarily produced in fast-twitch muscle fibers and oxidized in slow-twitch muscle fibers. Lactate is transported across the plasma membrane via proton-linked MCTs.3,4 Among the 14 MCT proteins, MCT1 and MCT4 appear to be the most important in skeletal muscles.5,6 Monocarboxylate transporter 1 is involved in the uptake of lactate by myocytes, and its expression is highly correlated with muscle oxidative capacity.7 On the other hand, MCT4 is involved in the release of lactate from myocytes, and its expression is associated with muscle glycolytic capacity.8
It is known that lactate transport and the levels of MCT protein expression in muscles change in accordance with metabolic demands in mammals. For example, the expression levels of MCT1 and MCT4 in the skeletal muscle increase after endurance and sprint training in rats and humans.9,10 Although changes in expression levels of MCTs during training have been evaluated, few studies11–14 have investigated the changes in MCTs in horses during development, despite the fact that growth is known to cause various alterations in muscle metabolism. In a cross-sectional study,15 we have shown that during development in rats, the expressions of MCT1 in the heart and soleus muscles increase but that of MCT4 in those muscles decreases with age. However, to our knowledge, longitudinal studies of the changes in amounts of MCTs in muscle have not been conducted hitherto.
Horses are suitable animals for use in a longitudinal study because muscle samples can be repeatedly collected from the same site. Results of a previous study13 indicated that the body weight of Thoroughbreds at the age of 24 months is almost equivalent to that of adults, and that the proportion of type IIA fibers in the GMM increases from the age of 2 months to 24 months because of the transition of type IIX fibers to type IIA fibers during the growth period. Also, it is known that in horses, the activities of CS and 3-hydroxyacyl-coenzyme A dehydrogenase increase with age during the growth phase.11,13 Moreover, it has been indicated that the maximal oxygen uptake in horses increases from 18 to 24 months of age.12 These data suggest that horses acquire muscle oxidative capacity as they grow. Peroxisome proliferator-activated receptor-γ coactivator-1α appears to be a key regulator of energy metabolism on the basis of the fact that it is a transcription coactivator that interacts with a broad range of transcription factors.16,17 In mouse cardiac myocytes, the transient expression of the PGC-1α gene induces an increase in mitochondrial gene expressions.18 In other studies,19,20 the overexpression of muscle-specific PGC-1α in transgenic mice led to enhanced mitochondrial biogenesis and the formation of slow-twitch fibers. Furthermore, because PGC-1α is associated with MCT1 expression, PGC-1α may influence lactate metabolism.21 However, the effect of growth on the expression of PGC-1α in horses is also unknown. The purpose of the study reported here was to undertake longitudinal analysis of the changes in MCT1 and MCT4 content and in indicators of energy metabolism in the GMM of Thoroughbreds during growth.
Gluteus medius muscle LDH Lactate dehydrogenase
Monocarboxylate transporter PGC-1α Peroxisome proliferator-activated receptor-γ coactivator-1α
Operon, Tokyo, Japan.
Calbiochem, San Diego, Calif.
DC Protein Assay, Bio-Rad, Hercules, Calif.
BioDynamics Laboratory Inc, Tokyo, Japan.
Hybond-P PVDF transfer membranes, Amersham Biosciences, Piscataway, NJ.
Amersham Biosciences, Piscataway, NJ.
Chemidoc system, Bio-Rad, Hercules, Calif.
Quantity One software, version 4.6.1, Bio-Rad, Hercules, Calif.
Beckman Paragon LD, Beckman Instruments Inc, La Brea, Calif.
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