After a Century, it's time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling is an important component of intermediary metabolism in vivo. Cell-Cell and intracellular Lactate Shuttles fulfill purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal and satiety signaling has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristic such as improved physical work capacity, metabolic flexibility, learning, and memory. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signaling and shuttling are dysregulated as occur in particular illnesses and injuries. Like a Phoenix, lactate has risen to major importance in 21 st Century Biology.
Peroxiredoxin 6 (Prdx6, 1-cys peroxiredoxin) is a unique member of the peroxiredoxin family that, in contrast to other mammalian peroxiredoxins, lacks a resolving cysteine and uses glutathione and π glutathione S-transferase to complete its catalytic cycle. Prdx6 is also the only peroxiredoxin capable of reducing phospholipid hydroperoxides through its glutathione peroxidase (Gpx) activity. In addition to its peroxidase activity, Prdx6 expresses acidic calcium-independent phospholipase A2 (aiPLA2) and lysophosphatidylcholine acyl transferase (LPCAT) activities in separate catalytic sites. Prdx6 plays crucial roles in lung phospholipid metabolism, lipid peroxidation repair, and inflammatory signaling. Here, we review how the distinct activities of Prdx6 are regulated during physiological and pathological conditions, in addition to the role of Prdx6 in cellular signaling and disease.
Several measured differences are the largest reported between MZ twins (TT expressed 55% more MHC I fibers, 12.4 ml/kg/min greater VOmax, and 8.6% lower body fat% vs. UT). These data collectively (a) support utilizing chronic endurance training to improve body composition and cardiovascular health and (b) suggest the cardiovascular and skeletal muscle systems exhibit greater plasticity than previously thought, further highlighting the importance of studying MZ twins with large (long-term) differences in exposomes.
Single muscle fiber sodium dodecyl sulfate polyacrylamide gel-electrophoresis (SDS-PAGE) is a sensitive technique for determining skeletal muscle myosin heavy chain (MHC) composition of human biopsy samples. However, the number of fibers suitable to represent fiber type distribution via this method is undefined. Muscle biopsies were obtained from the vastus lateralis (VL) of nine resistance-trained males (25 ± 1 year, height = 179 ± 5 cm, mass = 82 ± 8 kg). Single fiber MHC composition was determined via SDS-PAGE. VL fiber type distribution [percent MHC I, I/IIa, IIa, IIa/IIx, and total "hybrids" (i.e. I/IIa + IIa/IIx)] was evaluated according to number of fibers analyzed per person (25 vs. 125). VL fiber type distribution did not differ according to number of fibers analyzed (P > 0.05). VL biopsy fiber type distribution of nine subjects is represented by analyzing 25 fibers per person. These data may help minimize cost, personnel-time, and materials associated with this technique, thereby improving fiber typing efficiency in humans.
Perinatal transmission of hepatitis B virus is associated with substantial morbidity and mortality, yet controversy still exists regarding the value of routine screening of pregnant women in the United States and subsequent immunization of their at-risk neonates. To evaluate the cost-effectiveness of such a screening and immunization program, we developed a decision analysis model and obtained data from published reports, chart review, and a Delphi survey to determine outcome probabilities and costs. When considering direct and indirect costs, routine screening and immunization would be cost-effective at a prevalence of 0.06%, significantly lower than the national prevalence of 0.2%. At an annual national birth rate of 3.5 million births, a national policy of routine screening of all pregnant women would result in an annual net savings of more than $105 million. In the high-risk groups, as many as 140 cases of acute neonatal hepatitis and as many as 1400 cases of chronic liver disease would be prevented yearly per 100,000 pregnant women screened, at a net annual savings of as much as $765 million.
Several statistically and clinically relevant asymmetries were identified. The FT% differences between lower limbs were large and common. The findings also seem to conclude that DOM was stronger, moved faster, and contained more MHC I. However, only 23% of participants actually displayed that result. This highlights the need to analyze and report both group and individual data, particularly when interpreting findings across multiple related, but not necessarily causal, measurements.
Bagley, JR, Burghardt, KJ, McManus, R, Howlett, B, Costa, PB, Coburn, JW, Arevalo, JA, Malek, MH, and Galpin, AJ. Epigenetic responses to acute resistance exercise in trained vs. sedentary men. J Strength Cond Res 34(6): 1574–1580, 2020—Acute resistance exercise (RE) alters DNA methylation, an epigenetic process that influences gene expression and regulates skeletal muscle adaptation. This aspect of cellular remodeling is poorly understood, especially in resistance-trained (RT) individuals. The study purpose was to examine DNA methylation in response to acute RE in RT and sedentary (SED) young men, specifically targeting genes responsible for metabolic, inflammatory, and hypertrophic muscle adaptations. Vastus lateralis biopsies were performed before (baseline), 30 minutes after, and 4 hours after an acute RE bout (3 × 10 repetitions at 70% 1 repetition maximum [1RM] leg press and leg extension) in 11 RT (mean ± SEM: age = 26.1 ± 1.0 years; body mass = 84.3 ± 0.2 kg; leg press 1RM = 412.6 ± 25.9 kg) and 8 SED (age = 22.9 ± 1.1 years; body mass = 75.6 ± 0.3 kg; leg press 1RM = 164.8 ± 22.5 kg) men. DNA methylation was analyzed through methylation sensitive high-resolution melting using real-time polymerase chain reaction. Separate 2 (group) × 3 (time) repeated-measures analyses of variance and analyses of covariance were performed to examine changes in DNA methylation for each target gene. Results showed that acute RE (a) hypomethylated LINE-1 (measure of global methylation) in RT but not SED, (b) hypermethylated metabolic genes (GPAM and SREBF2) in RT, while lowering SREBF2 methylation in SED, and (c) did not affect methylation of genes associated with inflammation (IL-6 and TNF-α) or hypertrophy (mTOR and AKT1). However, basal IL-6 and TNF-α were lower in SED compared with RT. These findings indicate the same RE stimulus can illicit different epigenetic responses in RT vs. SED men and provides a molecular mechanism underpinning the need for differential training stimuli based on subject training backgrounds.
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