Effects of Endurance Training on Lactate Uptake Capacity and Its Related Proteins in Skeletal Muscles in Mice

Abstract

AimsLactate has been recognized not merely as an end product of glycolysis in skeletal muscle but also as an energy fuel. Lactate also acts as a signaling molecule for muscle mitochondrial biogenesis (Hashimoto et al., 2007; Hoshino et al., 2015; Kitaoka et al., 2016). Therefore, lactate uptake to skeletal muscles is important for using lactate as a fuel and as a signaling molecule. The lactate uptake is regulated by monocarboxylate transporter (MCT) and mitochondrial content in skeletal muscles. Muscle MCTs and mitochondrial content markers are increased after chronic endurance exercise training in humans and rodents. Therefore, we aimed □ to estimate parameters related to lactate uptake capacity using blood lactate concentrations in lactate tolerance test, and □ to examine the relationship between the parameters and the protein levels of MCTs and mitochondrial enzymes in mouse skeletal muscles after 3 weeks of endurance training.MethodsWe used C57BL/6J mice and divided them into two groups, control group (CON) and endurance training (15 ~ 25 m/min, 30 min/day, 5 days/week, 3 weeks) group (END). Lactate tolerance test was performed by lactate intraperitoneal (ip) injection (1 g/kg of body weight) 24h after the last bout of endurance training. We calculated area under the curve (AUC) and peak values of blood lactate concentration. Using the time‐series data of blood lactate concentration after ip injection, the parameter k and n in the following formula were estimated. d[lactate]/dt = k[lactate]nParameter estimation was performed using minimization of residual sum of squares between experimental and simulated data. Gastrocnemius muscles were harvested 24h after the lactate tolerance test. We measured protein levels of MCTs, mitochondrial electron transport chain protein (complex I~V), peroxisome proliferator‐activated‐receptor γ coactivator 1a (PGC‐1a), pyruvate dehydrogenase (PDH) and phospho‐fructokinase by Western blot.Results & DiscussionAUC and peak values of blood lactate concentration did not significantly differ between the two groups in the lactate tolerance test. Parameter k, which represents lactate uptake capacity, did not differ between the two groups. Muscle PGC1a was tended to be higher in the END than the CON (p = 0.095), but other protein levels did not significantly differ between the two groups. These results suggest that volume and/or duration of endurance training might not be enough. There was a positive correlation between the parameter k and protein levels of mitochondrial enzymes. This result suggests that the higher protein levels of mitochondrial enzymes in tricarboxylic acid cycle and electron transport chainin gastrocnemius muscles lead to the higher lactate uptake capacity. However, the relationship was not seen in the END. It is likely that lactate uptake capacity was associated with other factors in the early stage of endurance training.ConclusionLactate uptake capacity was closely related to protein levels of mitochondrial enzymes in skeletal muscles, but the relationship disappeared in the 3‐wk endurance‐trained mice.