The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.

Gi-coupled protein receptor 81 (GPR81) was first identified in adipocytes as a receptor for l-lactate, which upon binding inhibits cyclicAMP (cAMP)-protein kinase (PKA)-cAMP-response element binding (CREB) signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking. Muscle biopsies were obtained from healthy men and women at rest, after leg extension exercise, with or without venous infusion of sodium lactate, and 90 and 180 min after exercise (8 men and 8 women). Analyses included protein and mRNA levels of GPR81, as well as GPR81-dependent signaling molecules. GPR81 expression was 2.5-fold higher in type II glycolytic compared with type I oxidative muscle fibers, and the expression was inversely related to the percentage of type I muscle fibers. Muscle from women expressed about 25% more GPR81 protein than from men. Global PKA activity increased by 5%-8% after exercise, with no differences between trials. CREBS133 phosphorylation was reduced by 30% after exercise and remained repressed during the entire trials, with no influence of the lactate infusion. The mRNA expression of vascular endothelial growth factor (VEGF) and peroxisome-proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were increased by 2.5-6-fold during recovery, and that of lactate dehydrogenase reduced by 15% with no differences between trials for any gene at any time point. The high expression of GPR81-protein in type II fibers suggests that lactate functions as an autocrine signaling molecule in muscle; however, lactate does not appear to regulate CREB signaling during exercise.

Validity of ultrasonography-derived predictions for estimating skeletal muscle volume: a systematic literature review.

BACKGROUND: The amount of muscle volume (MV) varies between individuals and is important for health, well-being and performance. Therefore, the monitoring of MV using different imaging modalities is important. Magnetic resonance imaging (MRI) is considered the gold standard, but is not always easily accessible, and the examinations are expensive. Ultrasonography (US) is a much less expensive imaging method widely used to measure changes in muscle thickness (MT). Whether MT may translate into MV needs further investigation. PURPOSE: The aim of this review is to clarify whether US-derived equations based on MT predict MV based on MRI. METHODS: A systematic literature review was conducted according to the PRISMA statement, searching the electronic databases PubMed, CINAHL and Web of Science, for currently published equations to estimate MV with US. RESULTS: The literature search resulted in 363 citations. Twelve articles met the eligibility criteria. Ten articles scored eight out of eleven on QUADAS and two scored nine. Thirty-six prediction equations were identified. R values ranged between 0.53 and 0.961 and the standard error of the estimate (SEE) ranged between 6 and 12% for healthy adult populations, and up to 25.6% for children with cerebral palsy. Eight studies evaluated the results with a Bland-Altman plot and found no systematic errors. The overall strength and quality of the evidence was rated "low quality" as defined by the GRADE system. CONCLUSIONS: The validity of US-derived equations based on MT is specific to the populations from which it is developed. The agreement with MV based on MRI is moderate with the SEE ranging between 6 and 12% in healthy adult populations. Suggestions for future research include investigations as to whether testing positions or increasing the number of measuring sites could improve the validity for prediction equations.

Elevated plasma lactate levels via exogenous lactate infusion do not alter resistance exercise-induced signaling or protein synthesis in human skeletal muscle.

Lactate has been implicated as a potential signaling molecule. In myotubes, lactate incubation increases mechanistic target of rapamycin complex 1 (mTORC1)- and ERK-signaling and induces hypertrophy, indicating that lactate could be a mediator of muscle adaptations to resistance exercise. However, the potential signaling properties of lactate, at rest or with exercise, have not been explored in human tissue. In a crossover design study, 8 men and 8 women performed one-legged resistance exercise while receiving venous infusion of saline or sodium lactate. Blood was sampled repeatedly, and muscle biopsies were collected at rest and at 0, 90, and 180 min and 24 h after exercise. The primary outcomes examined were intracellular signaling, fractional protein synthesis rate (FSR), and blood/muscle levels of lactate and pH. Postexercise blood lactate concentrations were 130% higher in the Lactate trial (3.0 vs. 7.0 mmol/L, P < 0.001), whereas muscle levels were only marginally higher (27 vs. 32 mmol/kg dry wt, P = 0.003) compared with the Saline trial. Postexercise blood pH was higher in the Lactate trial (7.34 vs. 7.44, P < 0.001), with no differences in intramuscular pH. Exercise increased the phosphorylation of mTORS2448 (∼40%), S6K1T389 (∼3-fold), and p44T202/T204 (∼80%) during recovery, without any differences between trials. FSR over the 24-h recovery period did not differ between the Saline (0.067%/h) and Lactate (0.062%/h) trials. This study does not support the hypothesis that blood lactate levels can modulate anabolic signaling in contracted human muscle. Further in vivo research investigating the impact of exercised versus rested muscle and the role of intramuscular lactate is needed to elucidate its potential signaling properties.