Effects Of Lactate Administration Research Articles

Effects of lactate administration on hypertrophy and mTOR signaling activation in mouse skeletal muscle.

Lactate is a metabolic product of glycolysis and has recently been shown to act as a signaling molecule that induces adaptations in oxidative metabolism. In this study, we investigated whether lactate administration enhanced muscle hypertrophy and protein synthesis responses during resistance exercise in animal models. We used male ICR mice (7–8 weeks old) were used for chronic (mechanical overload induced by synergist ablation: [OL]) and acute (high‐intensity muscle contraction by electrical stimulation: [ES]) resistance exercise models. The animals were intraperitoneally administrated a single dose of sodium lactate (1 g/kg of body weight) in the ES study, and once a day for 14 consecutive days in the OL study. Two weeks of mechanical overload increased plantaris muscle wet weight (main effect of OL: p < 0.05) and fiber cross‐sectional area (main effect of OL: p < 0.05), but those were not affected by lactate administration. Following the acute resistance exercise by ES, protein synthesis and phosphorylation of p70 S6 kinase and ribosomal protein S6, which are downstream molecules in the anabolic signaling cascade, were increased (main effect of ES: p < 0.05), but lactate administration had no effect. This study demonstrated that exogenous lactate administration has little effect on the muscle hypertrophic response during resistance exercise using acute ES and chronic OL models. Our results do not support the hypothesis that elevated blood lactate concentration induces protein synthesis responses in skeletal muscle.

Effects of Lactate Administration on Mitochondrial Respiratory Function in Mouse Skeletal Muscle

Recent evidence has shown that mitochondrial respiratory function contributes to exercise performance and metabolic health. Given that lactate is considered a potential signaling molecule that induces mitochondrial adaptations, we tested the hypothesis that lactate would change mitochondrial respiratory function in skeletal muscle. Male ICR mice (8 weeks old) received intraperitoneal injection of PBS or sodium lactate (1 g/kg BW) 5 days a week for 4 weeks. Mitochondria were isolated from freshly excised gastrocnemius muscle using differential centrifugation and were used for all analyses. Lactate administration significantly enhanced pyruvate + malate- and glutamate + malate-induced (complex I-driven) state 3 (maximal/ATP synthesis-coupled) respiration, but not state 2 (basal/proton conductance) respiration. In contrast, lactate administration significantly decreased succinate + rotenone-induced (complex II-driven) state 3 and 2 respiration. No significant differences were observed in malate + octanoyl-l-carnitine-induced state 3 or 2 respiration. The enzymatic activity of complex I was tended to increase and those of complexes I + III and IV were significantly increased after lactate administration. No differences were observed in the activities of complexes II or II + III. Moreover, lactate administration increased the protein content of NDUFS4, a subunit of complex I, but not those of the other components. The present findings suggest that lactate alters mitochondrial respiratory function in skeletal muscle.

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes

IntroductionImpaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased...

Effect of lactate administration on mouse skeletal muscle under calorie restriction.

Calorie restriction (CR) involves a reductions of calorie intake without altering the nutritional balance, and has many beneficial effects, such as improving oxidative metabolism and extending lifespan. However, CR decreases in skeletal muscle mass and fat mass in correlation with the reduction in food intake. Lactate is known to have potential as a signaling molecule rather than a metabolite during exercise. In this study, we examined the effects of the combination of caloric restriction and lactate administration on skeletal muscle adaptation in order to elucidate a novel role of lactate. We first demonstrated that daily lactate administration (equivalent to 1 g/kg of body weight) for 2 weeks suppressed CR-induced muscle atrophy by activating mammalian/mechanistic target of rapamycin (mTOR) signaling, a muscle protein synthesis pathway, and inhibited autophagy-induced muscle degradation. Next, we found that lactate administration under calorie restriction enhanced mitochondrial enzyme activity (citrate synthase and succinate dehydrogenase) and the expression of oxidative phosphorylation (OXPHOS) protein expression. Our results suggest that lactate administration under caloric restriction not only suppresses muscle atrophy but also improves mitochondrial function.

Effect of lactate administration on exercise-induced PGC-1α mRNA expression in Thoroughbreds

The aim of this study was to examine the effects of lactate administration on the mRNA response of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) to acute exercise in Thoroughbred skeletal muscle. Five Thoroughbred horses performed treadmill running at 90% of maximal oxygen consumption for 2 min on two separate occasions, either after the administration of two litres of a sodium lactate solution (LAC; 500 mmol/l sodium lactate in 0.9% NaCl) or a saline solution as a control (CON; 0.9% NaCl). Lactate administration significantly elevated the peak plasma lactate concentration during exercise (16.0±2.8 mmol/l in LAC vs 10.8±2.2 mmol/l in CON). The increase in PGC-1α mRNA expression after 4 h of recovery from exercise was similar between treatments. However, there was positive correlation between exercise-induced PGC-1α mRNA response at 4 h after exercise and peak plasma lactate concentration during exercise. These results suggest that the exercise intensity-dependent adaptation of PGC-1α may be attributed, at least in part, to an increased lactate concentration.

Effects of lactate administration on mitochondrial enzyme activity and monocarboxylate transporters in mouse skeletal muscle.

Growing evidence shows that lactate is not merely an intermediate metabolite, but also a potential signaling molecule. However, whether daily lactate administration induces physiological adaptations in skeletal muscle remains to be elucidated. In this study, we first investigated the effects of daily lactate administration (equivalent to 1 g/kg of body weight) for 3 weeks on mitochondrial adaptations in skeletal muscle. We demonstrated that 3‐week lactate administration increased mitochondrial enzyme activity (citrate synthase, 3‐hydroxyacyl CoA dehydrogenase, and cytochrome c oxidase) in the plantaris muscle, but not in the soleus muscle. MCT1 and MCT4 protein contents were not different after 3‐week lactate administration. Next, we examined whether lactate administration enhances training‐induced adaptations in skeletal muscle. Lactate administration prior to endurance exercise training (treadmill running, 20 m/min, 60 min/day), which increased blood lactate concentration during exercise, enhanced training‐induced mitochondrial enzyme activity in the skeletal muscle after 3 weeks. MCT protein content and blood lactate removal were not different after 3‐week lactate administration with exercise training compared to exercise training alone. In a single bout experiment, lactate administration did not change the phosphorylation state of AMPK, ACC, p38 MAPK, and CaMKII in skeletal muscle. Our results suggest that lactate can be a key factor for exercise‐induced mitochondrial adaptations, and that the efficacy of high‐intensity training is, at least partly, attributed to elevated blood lactate concentration.

PO-074 Acute effects of lactate administration prior to endurance exercise on intramuscular signaling

Objective High-intensity exercise, which increases blood lactate concentration, is known as an effective method to induce mitochondrial biogenesis compared to traditional endurance exercise. In addition, it has been reported that lactate acts as a signaling molecule inducing mitochondrial biogenesis. Therefore, we hypothesized that efficacy of high-intensity exercise is partly induced by lactate. The purpose of this study was to investigate the effects of lactate administration on signaling related to mitochondrial biogenesis.&#x0D; Methods 8-week-old male ICR mice were used in this study. Mice were intraperitoneally administrated phosphate buffered saline (PBS) or 1 g/kg of body weight of sodium lactate. Immediately after the administration, mice were kept sedentary or performed treadmill exercise (20 m/min) for 60 min. Hence, there are the following four groups in this study: the PBS-sedentary, the Lactate-sedentary, the PBS-exercised and the Lactate-exercised. The blood, and the soleus and the plantaris muscles were harvested immediately after the rest or exercise. Nucleus and mitochondria were isolated to assess the localization of p53. Two-way ANOVA (Lactate x Exercise) was performed for statistical analysis.&#x0D; Results We first measured blood substrates and muscle glycogen concentrations. Lactate administration significantly increased blood lactate and plasma free fatty acid concentrations. Exercise significantly decreased glycogen concentration both in the soleus and the plantaris muscles. Furthermore, lactate administration significantly decreased muscle glycogen concentration only in the soleus muscle. To clarify the effects of lactate administration on intramuscular signaling, we assessed kinases related to mitochondrial biogenesis. Main effect of exercise was observed in phosphorylation state of AMPK, ACC, p38 MAPK, and CaMKII in the soleus and the plantaris muscles. There was a trend of negative effect of lactate in CaMKII phosphorylation in the soleus muscle. However, there was no effect of lactate administration on the other kinases. We also investigated phosphorylation and localization of p53. As a result, lactate administration tended to increase p53 phosphorylation in the plantaris muscle. However, p53 was not translocated to nucleus or mitochondria.&#x0D; Conclusions Lactate administration affected plasma FFA concentration and muscle glycogen concentration. However, acute lactate administration did not dramatically change intracellular signaling assessed in this study.

Effect of lactate administration on brain lactate levels during hypoglycemia in patients with type 1 diabetes

Administration of lactate during hypoglycemia suppresses symptoms and counterregulatory responses, as seen in patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), presumably because lactate can substitute for glucose as a brain fuel. Here, we examined whether lactate administration, in a dose sufficient to impair awareness of hypoglycemia, affects brain lactate levels in patients with normal awareness of hypoglycemia (NAH). Patients with NAH (n = 6) underwent two euglycemic-hypoglycemic clamps (2.8 mmol/L), once with sodium lactate infusion (NAH w|lac) and once with saline infusion (NAH w|placebo). Results were compared to those obtained during lactate administration in patients with IAH (n = 7) (IAH w|lac). Brain lactate levels were determined continuously with J-difference editing 1H-MRS. During lactate infusion, symptom and adrenaline responses to hypoglycemia were considerably suppressed in NAH. Infusion of lactate increased brain lactate levels modestly, but comparably, in both groups (mean increase in NAH w|lac: 0.12 ± 0.05 µmol/g and in IAH w|lac: 0.06 ± 0.04 µmol/g). The modest increase in brain lactate may suggest that the excess of lactate is immediately metabolized by the brain, which in turn may explain the suppressive effects of lactate on awareness of hypoglycemia observed in patients with NAH.

Effects Of Lactate Administration On Intracellular pH And Contractile Performance During Rhythmic Muscle Contractions

Effects Of Lactate Administration On Intracellular pH And Contractile Performance During Rhythmic Muscle Contractions