Muscle Lactate Metabolism Research Articles

Swim Training Affects on Muscle Lactate Metabolism, Nicotinamide Adenine Dinucleotides Concentration, and the Activity of NADH Shuttle Enzymes in a Mouse Model of Amyotrophic Lateral Sclerosis.

In this study, we aim to verify whether swim training can improve lactate metabolism, NAD+ and NADH levels, as well as modify the activity of glycolytic and NADH shuttle enzymes and monocarboxylate transporters (MCTs) in skeletal muscle of amyotrophic lateral sclerosis (ALS) mice. ALS mice (SOD1G93A) (n = 7 per group) were analyzed before the onset of ALS, at first disease symptoms (trained and untrained), and the last stage of disease (trained and untrained), and then compared with a wild-type (WT) group of mice. The blood lactate and the skeletal muscle concentration of lactate, NAD+ and NADH, MCT1 and MCT4 protein levels, as well as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activities in skeletal muscle were determined by fluorometric, Western blotting, liquid chromatography-MS3 spectrometry, and spectrometric methods. In the untrained terminal ALS group, there were decreased blood lactate levels (p < 0.001) and increased skeletal muscle lactate levels (p < 0.05) as compared with a WT group of mice. The amount of nicotinamide adenine dinucleotides in the ALS groups were also significantly reduced as well as LDH activity and the level of MCT1. Swim training increased lactate levels in the blood (p < 0.05 vs. ALS TERMINAL untrained). In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (p < 0.05). The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice.

Progression of Cancer Cachexia Alters Muscle Lactate Metabolism In ApcMin/+ Mice

Roughly 100,000 individuals are diagnosed with colorectal cancer a year, 80% of these cases arise from adenomatous polyps. A mutation of the tumor suppressor gene, Adenomatous polyposis coli (Apc) results in multiple intestinal neoplasia (Min), thus the Apc (Min/+) mouse is a common colorectal cancer model. Cancer cells favor a highly glycolytic environment. As such, there is an induction of processes regulating lactate metabolism and lactate shuttling. How colorectal cancer influences skeletal muscle lactate metabolism is uncertain. Purpose: We investigated how muscle lactate metabolism is regulated during the progression of cancer cachexia in Apc (Min/+) mice. Methods: Male Min/+mice (n = 17) were classified by body mass loss: weight stable (WS, 蠄 5%, n = 5), and cachectic (CC, 6‐19%; n = 5). C57BL/6J (B6, n = 6) served as controls. Quadriceps muscle samples were extracted and real‐time PCR was conducted to quantify lactate‐related gene expression. Results: LDH‐A was reduced 47% in the CC mice compared to the WS mice (p &lt; 0.05), while LDH‐B was not changed with cancer cachexia progression (p = 0.09). Monocarboxylate transporter 1 (MCT1) was induced 1.9‐fold in CC mice (p &lt; 0.05) compared to the B6 mice. MCT4 was induced 1.7‐fold and 2.3‐fold in the CC mice compared to B6 and WS mice, respectively. Muscle CD147 was not changed with cancer cachexia progression (p = 0.31).ConclusionThe progression of cachexia in mice with colon cancer alters markers of lactate metabolism that may play a role in muscle wasting associated with cachexia.

Exercise–related muscle lactate metabolism in zebrafish juveniles: The effect of early life temperature

The accumulation of lactate in fish muscles during exercise and particularly its decomposition rate afterwards is a process of great importance, as it significantly influences swimming capacity. In the present study, zebrafish juveniles were reared at different water temperatures (22°C, 25°C, 28°C and 31°C) and before being subjected to the swimming trials (according to Brett's method) they were acclimated to a common intermediate temperature of 26.5°C for 45 days. Muscle lactate concentration was estimated on 35 specimens per temperature origin, which were sampled at the following time periods: at rest, after full exhaustion due to swimming and after recovery for thirty minutes, one hour, three hours, six hours and nine hours. Lactate analysis revealed that in all cases, lactate metabolism follows that previously described for other species patterns, since its concentration rises during exercise and decreases during the recovery time. It was also shown that developmental temperature affects not only the initial and final lactate concentration (at rest and at full exhaustion respectively), but its decomposition rate during recovery as well since the 22°C-reared fish require considerably more time than the others in order to fully recover and the 31°C-reared fish present the fastest recovery among all. Developmental temperature during the early life stages is once again proven to play an important role in the subsequent life of the fish.

Effects of endotoxin on lactate metabolism in humans

IntroductionHyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge.MethodsFourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose.ResultsIn both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged.ConclusionsLPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production.Trial registrationClinicalTrials.gov NCT01647997

Metabolismo do lactato: uma revisão sobre a bioenergética e a fadiga muscular

The purpose of this study was to present the main events regarding the muscle lactate metabolism to aid the understanding about utilization of the blood lactate concentrations (BLC) on the estimative of lactic anaerobic metabolism and its likely relationship to the acute muscle fatigue. Traditionally, the increase of BLC was associated to the insufficient mitochondrial O2 supply. However, recent studies showed that increase of BLC can be due the action of another agent such as epinephrine and inorganic phosphate. In the same way, the relationship between BLC and acute muscle fatigue has been supported by increase in cellular acidosis. Nevertheless, recent studies have shown that cellular acidosis can restore the force in isolated and electrically stimulated muscle fibers. These findings suggest that utilization of the BLC on the estimative of lactic anaerobic metabolism should be used with caution and the relationship between BLC and acute muscle fatigue can only be a casual phenomenon.

Lactate kinetics in human tissues at rest and during exercise

Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during exercise is much debated. In the early days skeletal muscle was mainly seen as the site of lactate production during contraction and lactate production associated with a lack of muscle oxygenation and fatigue. Later it was recognized that skeletal muscle not only played an important role in lactate production but also in lactate clearance and this led to a renewed interest, not the least from the Copenhagen School in the 1930s, in the metabolic role of lactate in skeletal muscle. With the introduction of lactate isotopes muscle lactate kinetics and oxidation could be studied and a simultaneous lactate uptake and release was observed, not only in muscle but also in other tissues. Therefore, this review will discuss in vivo human: (1) skeletal muscle lactate metabolism at rest and during exercise and suggestions are put forward to explain the simultaneous lactate uptake and release; and (2) lactate metabolism in the heart, liver, kidneys, brain, adipose tissue and lungs will be discussed and its potential importance in these tissues.

200th Anniversary of Lactate Research in Muscle

This year, 2008, marks the bicentennial of research into lactate metabolism in muscle. Berzelius linked lactate accumulation to exercise in 1807/1808 when he noted the presence of lactate in the muscles of "hunted stags." Today, the exact mechanism of intramuscular lactate oxidation and the relationship of lactate dehydrogenase to mitochondria remain unresolved as animated debate surrounds the intracellular lactate shuttle.

Muscle and Liver Lactate Metabolism in Haart-Treated and Naive HIV-Infected Patients: The Mitovir Study

To assess the impact of nucleoside analogue reverse transcriptase inhibitor (NRTI) combination therapy on muscle and liver lactate metabolism in HIV-infected patients. This cross-sectional study involved HIV-infected patients who were either antiretroviral-naive (Group 1) or were receiving either a stable triple-drug combination including at least one d-drug (zidovudine, zalcitabine, stavudine, didanosine; Group 2) or a backbone of abacavir and lamivudine (Group 3). Lactataemia was measured at rest. Muscle lactate metabolism was assessed during a standardized exercise test and liver lactate metabolism during intravenous lactate infusion. Mitochondrial DNA was quantified in peripheral blood mononuclear cells. A total of 65 patients were enrolled (16, 31 and 18 patients in Group 1, Group 2 and Group 3, respectively). None of the patients had symptoms of hyperlactataemia. Patients in Group 3 had received d-drugs for a median of seven years before switching to abacavir and lamivudine. Median baseline lactataemia, although within the normal range, was significantly higher in both treatment groups than in the naive patients (Group 2: 1.4, Group 3: 1.5, and Group 1: 1.0 mmol/l, P = 0.005). Muscle lactate clearance was significantly lower in both treatment groups than in naive patients (Group 2: 1.6, Group 3: 1.8, and Group 1: 2.1, P = 0.01). Lactate liver metabolism and mitochondrial DNA levels did not differ among the three groups. In HIV-infected patients without symptomatic hyperlactataemia, all NRTI-containing HAART regimens appear to cause muscle mitochondrial damage but to spare the liver. Absence of difference between Group 2 and Group 3 raises questions about the potential reversibility of muscle mitochondrial dysfunction, and/or the ability of abacavir and lamivudine to induce such mitochondrial damage.

Lactate as a fuel for mitochondrial respiration

Lactate production in skeletal muscle has now been studied for nearly two centuries and still its production and functional role at rest and during muscle contraction is a subject of debate. Historically, skeletal muscle was seen mainly as the site of lactate production during contraction and lactate production associated with a lack of muscle oxygenation and fatigue. Later, it was recognized that skeletal muscle not only plays an important role in lactate production but also in lactate clearance and this in turn has led to a renewed interest in the metabolic fate of lactate in skeletal muscle and also in other tissues. Studies using lactate isotopes have shown that skeletal muscle extracts lactate from the circulation despite a substantial net lactate release, and that skeletal muscle has a large capacity for lactate oxidation; these processes being enhanced with exercise. Lactate dehydrogenase (LDH) controls the formation of lactate and may regulate the turnover of lactate in the muscle cell. Skeletal muscle contains five LDH isoforms (LDH1-5). Of the five LDH isoforms, the heart-specific LDH1, 2 is generally suggested to favour the reaction of lactate to pyruvate whereas the muscle-specific LDH4,5 isoform favours lactate formation. However, in this paper, it is argued that compartmentalization of the muscle cell and LDH association with cell structures may play a more predominant role in whether the LDH reaction proceeds towards lactate or pyruvate formation. The model for skeletal muscle lactate metabolism presented is in essence based on a synthesis of old and more recent studies on skeletal muscle lactate transport, uptake, release, oxidation, and the role of LDH at rest and during exercise.

Alpha 2-adrenergic agonists increase cellular lactate efflux.

We reported previously that genetic polymorphisms of the alpha 2-adrenergic receptor are associated with hyperinsulinemia, diabetes mellitus, and hypertension in blacks. The evolutionary driving force for maintaining such deleterious mutations in the black population is unknown. Recognizing that vascular alpha 2-adrenergic receptors mediate cold-induced vasoconstriction and that temperature maintenance is a primary thrust of cellular metabolism, we postulated that vascular alpha 2-adrenergic receptors contribute significantly to metabolic heat generation in homeotherms such as humans. Using aerobic lactate production as an indicator of thermogenesis, we measured metabolic heat production in HT29 cells that expressed the gene encoding human vascular alpha 2-adrenergic receptors. Epinephrine, an alpha 2-adrenergic receptor agonist, increased net lactate efflux from 226 +/- 20 to 280 +/- 20 nmol/min (mean +/- SE) (P = .06). Clonidine, a more specific alpha 2-adrenergic agonist, increased lactate efflux from 110 +/- 6 to 156 +/- 8 nmol/min (P < .01). Similarly, in the presence of physiological concentrations of glucose (5.5 mmol/L), insulin increased lactate production from 123 +/- 6 to 175 +/- 10 nmol/min (P < .01). Because differences in aerobic glycolysis may also explain the heat intolerance and abnormal fuel homeostasis found in genetically hypertensive rats, we also measured lactate production in cultured vascular smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar-Kyoto rats (WKY). Vascular smooth muscle cells from SHRSP had significantly greater lactate efflux compared with cells from normotensive WKY (296 +/- 4 versus 172 +/- 2 nmol/min, P < .001). These differences were not due to abnormalities in glucose uptake, as lactate efflux was greater in SHRSP cells compared with WKY cells when dextrose was replaced with equimolar concentrations of fructose (230 +/- 6 versus 138 +/- 2 nmol/min, P < .001). alpha 2-Adrenergic agonists increase lactate efflux in HT29 cells, and abnormalities in vascular smooth muscle lactate metabolism in genetically hypertensive rats is independent of altered glucose uptake. These data provide support for our hypothesis that balanced polymorphisms of the alpha 2-adrenergic receptor could offer protection against cold stress by increasing the thermogenic response associated with aerobic lactate production.

Muscle lactate metabolism in recovery from intense exhaustive exercise: impact of light exercise

This study examined the effect of low-intensity exercise on lactate metabolism during the first 10 min of recovery from high-intensity exercise. Subjects exercised (61.0 +/- 5.4 W) one leg to exhaustion (approximately 3.5 min), and after 1 h of rest they performed the same exhaustive exercise with the other leg. For one leg the intense exercise was followed by rest [passive (P) leg], and for the other leg the exercise was followed by a 10-min period with low-intensity exercise at a work rate of 10 W [active (A) leg]. The muscle lactate concentration after the intense exercise was the same in the P and A legs, but after 10 min of recovery, the lactate concentration and the arterial blood lactate level were higher for the P leg than for the A leg (both P < 0.05). During the recovery, the mean blood flow was lower for the P leg than for the A leg (P < 0.05), whereas the mean lactate efflux was not significantly different. During the 10 min of recovery, lactate release accounted for approximately 60% of the change in muscle lactate for either leg. The leg excess postexercise O2 consumption during 10 min of recovery was 440 and 750 ml for the P and A legs, respectively. The present data suggest that a lowered blood lactate level during active recovery is due to an elevated muscle lactate metabolism and is not caused by a transient higher release of lactate from the exercising muscles coupled with greater uptake in other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate turnover at rest and during submaximal exercise in patients with heart failure

Systemic and lower limb skeletal muscle lactate metabolism was studied in 10 men with congestive heart failure by use of a primed continuous intravenous infusion of L-(+)-[U-14C]lactate. Arterial and deep femoral venous blood samples were obtained at rest and during 30 min of submaximal exercise. Systemic lactate metabolic turnover rate (Rd) was determined using Steele's isotopic steady-state equation (Rd = isotopic infusion rate/arterial specific activity). Plasma lactate concentrations in the artery and deep femoral vein did not change significantly from resting values during exercise (1.11 +/- 0.13 vs. 1.26 +/- 0.12 and 1.27 +/- 0.12 vs. 1.30 +/- 0.12 mM, respectively), whereas Rd increased from 22.5 +/- 1.8 to 41.6 +/- 4.8 mumol.kg-1.min-1 (P < 0.005). Rd did not significantly correlate with arterial lactate concentration during rest or exercise. Because of simultaneous uptake and release of lactate in skeletal muscle, arterial and deep femoral venous lactate concentrations are not closely related to either systemic or lower limb skeletal muscle lactate metabolism in patients with congestive heart failure.

Plasma catecholamine and corticosterone and their in vitro effects on lizard skeletal muscle lactate metabolism

Lizard skeletal muscles utilize primarily lactate as a gluconeogenic substrate for glycogen replenishment following exercise. To understand the influence of selected hormones on this process, we measured changes in plasma catecholamines and corticosterone resulting from exercise in the lizard Dipsosaurus dorsalis and then investigated the physiological effects of those hormones on skeletal muscle lactate and glucose metabolism in vitro. Plasma epinephrine (Epi), norepinephrine, and corticosterone (Cort) increased 5.8, 10.2, and 2.2 times, respectively, after 5 min of exhaustive exercise. Epi and Cort levels remained elevated after 2 h of recovery. Skeletal muscle fiber bundles isolated from the red and white regions of the iliofibularis muscle were incubated 2 h at 40 degrees C in the presence of postexercise concentrations of [14C]lactate (15 mM) and glucose (8.5 mM) in the presence and absence of Epi or Cort. Red muscle oxidized both substrates at 2-3 times the rate of white muscle, and both red and white fibers oxidized lactate at 5-10 times the rate of glucose oxidation. Epi had a stimulatory effect on lactate oxidation by white muscle. Lactate incorporation into glycogen proceeded at 2-3 times the rate of glucose incorporation in both muscle types, with rates in red muscle again 2-3 times that for white muscle. Epi stimulated lactate carbon incorporation into glycogen by 50-140% in both red and white muscle but had no effect on glucose incorporation into glycogen in either tissue. We interpret these data as evidence that epinephrine stimulates lactate removal by skeletal muscle. Cort had no effect on lactate metabolism in either muscle type.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood lactate levels do not closely reflect skeletal muscle lactate metabolism in congestive heart failure

Blood lactate levels do not closely reflect skeletal muscle lactate metabolism in congestive heart failure

Oxidative removal of lactate after strenuous exercise.

Metabolic fate of lactate after strenuous exercise which lasted 2-3 min was investigated in rats and mice. 14C-labeled lactate or glucose was injected into the aorta of rats through an catheter. 14C-glucose was injected intraperitoneally into the mice after supramaximal exercise. The mice ran twice with a 4 hr interval to investigate muscle 14C-lactate metabolism which was produced from muscle 14C-glycogen. A great deal of blood and muscle 14C-lactate was expired as 14CO2 after the exercise. The results indicate that oxidative removal is the major fate of lactate metabolism after strenuous exercise and that blood glucose is the major substrate for muscle glycogen resynthesis. Light intensity exercise after strenuous exercise (active recovery) enhances oxidative removal of blood and muscle lactate. Gluconeogenesis from lactate to glycogen within the skeletal muscle is not a major pathway of muscle lactate metabolism, while high intensity training can activate this pathway.

Dichloroacetate inhibits glycolysis and augments insulin-stimulated glycogen synthesis in rat muscle.

The decrease in plasma lactate during dichloroacetate (DCA) treatment is attributed to stimulation of lactate oxidation. To determine whether DCA also inhibits lactate production, we measured glucose metabolism in muscles of fed and fasted rats incubated with DCA and insulin. DCA increased glucose-6-phosphate, an allosteric modifier of glycogen synthase, approximately 50% and increased muscle glycogen synthesis and glycogen content greater than 25%. Lactate release fell; inhibition of glycolysis accounted for greater than 80% of the decrease. This was associated with a decrease in intracellular AMP, but no change in citrate or ATP. When lactate oxidation was increased by raising extracellular lactate, glycolysis decreased (r = - 0.91), suggesting that lactate oxidation regulates glycolysis. When muscle lactate production was greatly stimulated by thermal injury, DCA increased glycogen synthesis, normalized glycogen content, and inhibited glycolysis, thereby reducing lactate release. The major effect of DCA on lactate metabolism in muscle is to inhibit glycolysis.

Insulin-like effects of puromycin on lactate metabolism in frog skeletal muscle

1. 1. Experiments were carried out to determine whether puromycin in a concentration sufficient to block protein synthesis also blocks the stimulating effect of insulin on the oxidation and incorporation into glycogen of lactate in frog skeletal muscle. 2. 2. In the absence of added substrate, puromycin blocked the stimulating action of insulin on O 2 consumption, but in the presence of added lactate puromycin stimulated the oxidation of lactate and its incorporation into glycogen. Thus puromycin had effects similar to those of insulin on lactate metabolism in muscle. The effects of the two substances together were additive.