Genetic evidence for involvement of ß2-adrenergic receptor in brown adipose tissue thermogenesis in humans.

BACKGROUND: Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes of the ß-adrenergic receptor (AR), as well as effects of its genetic variants on functions of BAT, remains unclear in humans. We conducted association analyses of genes encoding ß-ARs and BAT activity in human adults. METHODS: Single nucleotide polymorphisms (SNPs) in ß1-, ß2-, and ß3-AR genes (ADRB1, ADRB2, and ADRB3) were tested for the association with BAT activity under mild cold exposure (19 °C, 2 h) in 399 healthy Japanese adults. BAT activity was measured using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). To validate the results, we assessed the effects of SNPs in the two independent populations comprising 277 healthy East Asian adults using near-infrared time-resolved spectroscopy (NIRTRS) or infrared thermography (IRT). Effects of SNPs on physiological responses to intensive cold exposure were tested in 42 healthy Japanese adult males using an artificial climate chamber. RESULTS: We found a significant association between a functional SNP (rs1042718) in ADRB2 and BAT activity assessed with FDG-PET/CT (p < 0.001). This SNP also showed an association with cold-induced thermogenesis in the population subset. Furthermore, the association was replicated in the two other independent populations; BAT activity was evaluated by NIRTRS or IRT (p < 0.05). This SNP did not show associations with oxygen consumption and cold-induced thermogenesis under intensive cold exposure, suggesting the irrelevance of shivering thermogenesis. The SNPs of ADRB1 and ADRB3 were not associated with these BAT-related traits. CONCLUSIONS: The present study supports the importance of ß2-AR in the sympathetic regulation of BAT thermogenesis in humans. The present collection of DNA samples is the largest to which information on the donor's BAT activity has been assigned and can serve as a reference for further in-depth understanding of human BAT function.

Effects of Exercise Training on Cardiac and Skeletal Muscle Functions in Patients with Chronic Heart Failure.

The primary symptom in patients with chronic heart failure (CHF) is exercise intolerance. Previous studies have reported that reduced exercise tolerance in CHF can be explained not only by cardiac output (a central factor) but also by reduced skeletal muscle aerobic capacity (a peripheral factor). Although exercise training in CHF improves exercise tolerance, few studies have evaluated the effects of exercise training on each specific central and peripheral factor in CHF. The aim of this study was to investigate the central and peripheral aerobic functions in CHF and the effects of exercise training in CHF on cardiac output and skeletal muscle deoxygenation during exercise. We assessed peak oxygen uptake (VO2) during cardiopulmonary exercise testing, peak cardiac output (CO) using noninvasive hemodynamic monitoring, and muscle oxygen saturation (SmO2) using near-infrared spectroscopy (NIRS). Patients with CHF were trained for 12 weeks and performed ramp cycling exercise until exhaustion before and after the exercise training. Peak VO2, peak CO, and SmO2 changes from rest to peak exercise (ΔSmO2) were significantly lower in CHF than those in healthy subjects. As a result of exercise training, peak oxygen uptake in patients with CHF was improved and positively associated with change in ΔSmO2. In contrast, there was no change in peak cardiac output. The results of this study indicate that both cardiac and skeletal muscle functions in patients with CHF were lower than those in healthy subjects. Further, the results suggest that the improvement of exercise capacity in patients with CHF by exercise training was related to the improved utilization of oxygen (a peripheral factor) in skeletal muscle.

Reduced Scattering Coefficient During Incremental Exercise Is Constant Without Being Affected by Changes in Muscle Oxygenation or Hemodynamics.

Previous studies have reported that the reduced scattering coefficient (µs') in the vastus lateralis changes during ramp-incremental exercise due to blood volume changes or accumulation of metabolic by-products. We aimed to clarify the influences of deoxygenation and blood volume changes during exercise on µs' dynamics in subjects with various aerobic capacities. Twenty-three healthy young men participated in this study. All subjects performed a ramp-incremental cycling exercise until exhaustion and were divided into two groups: lower (Low: n = 12; peak pulmonary oxygen uptake per kg of fat-free mass (VO2peak), 54.2 ± 5.3 mL/kg/min) and higher aerobic capacity group (High: n = 11; VO2peak, 69.7 ± 5.2 mL/kg/min) by median of VO2peak. Deoxygenated hemoglobin and myoglobin concentrations (deoxy[Hb + Mb]) and total [Hb + Mb] (total[Hb + Mb]) in the vastus lateralis were monitored during the exercise by three-wavelength (760, 800, and 830 nm) time-resolved NIRS. Similarly, µs' at each wavelength was continuously monitored. With increasing exercise intensity, deoxy[Hb + Mb] and total[Hb + Mb] significantly increased in both groups, and the average values of the peak amplitudes of deoxy[Hb + Mb] and total[Hb + Mb] during exercise showed a 106.4% increase and a 17.9% increase from the start of the exercise, respectively. Furthermore, the peak amplitude of total[Hb + Mb] was significantly greater in High. Conversely, there were no changes in µs' at any wavelength during exercise and no differences between two groups, suggesting that the great deoxygenation and blood volume changes during incremental exercise have little effect on µs' dynamics.

Relationships between plasma lipidomic profiles and brown adipose tissue density in humans.

BACKGROUND/OBJECTIVES: The thermogenic function of brown adipose tissue (BAT) is generally activated in winter and tightly regulated through various metabolic processes. However, the mechanisms mediating these changes have not been elucidated in humans. Here, we investigated the relationships between BAT density (BAT-d) and lipid metabolites in plasma from men and women in the winter and summer. SUBJECTS/METHODS: In total, 92 plasma samples were obtained from 23 men and 23 women, aged 21-55 years, on two different occasions (summer and winter). Lipid metabolites were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. BAT-d was evaluated by measuring total hemoglobin concentrations in the supraclavicular region using near-infrared time-resolved spectroscopy. Anthropometric parameters, such as the percentage of whole body fat and visceral fat area (VFA), were evaluated. Factors influencing BAT-d were investigated by univariate and multivariate regression analyses. RESULTS: A variety of metabolite peaks, such as glycerophospholipids (168 peaks), steroids and derivatives (78 peaks), fatty acyls (62 peaks), and glycerolipids (31 peaks), were detected. Univariate regression analysis, corrected by false discovery rate to yield Q values, revealed significant correlations in BAT-d and phosphatidylethanolamine (PE(46:2), r = 0.62, Q = 4.9 × 10-2) in the summer, androgens (r = 0.75, Q = 7.0 × 10-3) in the winter, and diacylglycerol (DG(36:1), r = -0.68, Q = 4.9 × 10-2) in the summer in men, but not in women. Multivariate regression analysis in the winter revealed a significant correlation between BAT-d and plasma androgens (P = 5.3 × 10-5) in men and between BAT-d and VFA (P = 2.2 × 10-3) in women. CONCLUSIONS: Certain lipids in plasma showed unique correlations with BAT-d depending on sex and season. BAT-d showed a specific correlation with plasma androgens in men in the winter.

Reduced Optical Path Length in the Vastus Lateralis During Ramp Cycling Exercise.

Near-infrared time-resolved spectroscopy (NIRTRS) can quantitatively evaluate mean optical path length (MPL). Since an increase in optical absorbers in the NIR region (e.g. an increase in deoxygenated hemoglobin during exercise) would shorten the MPL, the NIRS measurement area may vary depending on physical and physiological characteristics of the measurement region and/or the exercise intensity. The aim of this study was to examine the changes in MPL measured by NIRTRS during ramp cycling exercise between fat layer thickness-matched subjects with different aerobic capacities. Healthy control (CON, n = 8) and endurance-trained males (TR, n = 8) performed ramp cycling exercise until exhaustion. Deoxygenated hemoglobin concentration (Deoxy-Hb), total hemoglobin concentration (Total-Hb) and oxygenated hemoglobin concentration (Oxy-Hb) were evaluated by a three-wavelength NIRTRS system. MPL in each wavelength (MPL760, MPL800 and MPL830) was monitored continuously. With increasing exercise intensity, Total- and Deoxy-Hb significantly increased and Oxy-Hb decreased in both groups. Total- and Oxy-Hb during exercise were significantly higher in TR than CON (P < 0.05, P < 0.01, respectively). Furthermore, Deoxy-Hb also tended to be higher in TR than CON (P = 0.07). In addition, MPL at all wavelengths significantly shortened with an increase in exercise intensity, with no differences between CON and TR. In particular, MPL760 at peak exercise shortened more than 10% compared to the start of exercise in both groups, even though MPL830 decreased only a few per cent. These findings suggest that the NIRS measurement area may be reduced during ramp cycling exercise due to shortened MPL. Additionally, the changes in MPL may be especially greater at 760 nm than at the other wavelengths due to greater changes in Deoxy-Hb during exercise. Furthermore, this study indicates that the measurements of muscle deoxygenation using continuous-wave NIRS can be less accurate since they are significantly affected by changes in the optical path length.

Applicability of Supraclavicular Oxygenated and Total Hemoglobin Evaluated by Near-Infrared Time-Resolved Spectroscopy as Indicators of Brown Adipose Tissue Density in Humans.

Brown adipose tissue (BAT) may potentially be used in strategies for preventing lifestyle-related diseases. We examine evidence that near-infrared time-resolved spectroscopy (NIRTRS) is capable of estimating human BAT density (BAT-d). The parameters examined in this study are total hemoglobin [total-Hb]sup, oxygenated Hb [oxy-Hb]sup, deoxygenated Hb [deoxy-Hb]sup, Hb O2 saturation (StO2sup), and the reduced scattering coefficient in the supraclavicular region (µs'sup), where BAT deposits can be located; corresponding parameters in the control deltoid region are obtained as controls. Among the NIRTRS parameters, [total-Hb]sup and [oxy-Hb]sup show region-specific increases in winter, compared to summer. Further, [total-Hb]sup and [oxy-Hb]sup are correlated with cold-induced thermogenesis in the supraclavicular region. We conclude that NIRTRS-determined [total-Hb]sup and [oxy-Hb]sup are useful parameters for evaluating BAT-d in a simple, rapid, non-invasive manner.

Impact of Six Consecutive Days of Sprint Training in Hypoxia on Performance in Competitive Sprint Runners.

Kasai, N, Mizuno, S, Ishimoto, S, Sakamoto, E, Maruta, M, Kurihara, T, Kurosawa, Y, and Goto, K. Impact of six consecutive days of sprint training in hypoxia on performance in competitive sprint runners. J Strength Cond Res 33(1): 36-43, 2019-The purpose of this study was to determine the effects of 6 successive days of repeated sprint (RS) training in moderate hypoxia on anaerobic capacity in 100-200-m sprint runners. Eighteen male sprint runners (age, 20.0 ± 0.3 years; height, 175.9 ± 1.1 cm; and body mass, 65.0 ± 1.2 kg) performed repeated cycling sprints for 6 consecutive days in either normoxic (NOR; fraction of inspired oxygen [FiO2], 20.9%; n = 9) or hypoxic conditions (HYPO; FiO2, 14.5%; n = 9). The RS ability (10 × 6-second sprints), 30-second maximal sprint ability, maximal oxygen uptake ((Equation is included in full-text article.)max), and 60-m running time on the track were measured before and after the training period. Intramuscular phosphocreatine (PCr) content (quadriceps femoris muscle) was measured by P-magnetic resonance spectroscopy (P-MRS) before and after the training period. Both groups showed similar improvements in RS ability after the training period (p < 0.05). Power output during the 30-second maximal sprint test and (Equation is included in full-text article.)max did not change significantly after the training period in either group. Running time for 0-10 m improved significantly after the training period in the HYPO only (before, 1.39 ± 0.01 seconds; after, 1.34 ± 0.02 seconds, p < 0.05). The HYPO also showed a significant increase in intramuscular PCr content after the training period (before, 31.5 ± 1.3 mM; after, 38.2 ± 2.8 mM, p < 0.05). These results suggest that sprint training for 6 consecutive days in hypoxia or normoxia improved RS ability in competitive sprint runners.

Partial Range of Motion Exercise Is Effective for Facilitating Muscle Hypertrophy and Function Through Sustained Intramuscular Hypoxia in Young Trained Men.

Goto, M, Chikako, M, Hirayama, T, Terada, S, Nirengi, S, Kurosawa, Y, Nagano, A, and Hamaoka, T. Partial range of motion exercise is effective for facilitating muscle hypertrophy and function through sustained intramuscular hypoxia in young trained men. J Strength Cond Res 33(5): 1286-1294, 2019-The acute response to and long-term effects of partial range of motion exercise (PRE) and full range of motion exercise (FRE) of elbow extensors were compared in young trained men. The PRE was expected to increase the intramuscular hypoxic environment, which was theorized to enhance muscular hypertrophy. Forty-four resistance-trained men were divided into 2 training groups, PRE (n = 22) or FRE (n = 22) group, and performed the PRE or FRE acute exercise protocol. The PRE (elbow range from 45° to 90°) and FRE (from 0° to 120°) acute protocols consisted of 3 sets of 8 repetitions, with an 8RM, and an equivalent workload. After the initial testing, the training program for each group, comprised 3 training sessions per week for 8 weeks, was started. The acute responses of area under the oxygenated hemoglobin (Oxy-Hb) curve, blood lactate concentration, and root mean square of electromyography were significantly higher both before and after PRE than FRE training. Long-term effects were produced by both PRE and FRE, with significant (p ≤ 0.05) increases in cross-sectional area (CSA) of triceps brachii and isometric strength. The CSA increased significantly greater after PRE (48.7 ± 14.5%) than after FRE (28.2 ± 10.9%). Furthermore, during the PRE program, a positive correlation was detected between the percent increase in CSA and area under the Oxy-Hb curves before and after 8-week exercise training (before 8-week exercise training: r = 0.59, after 8-week exercise training: r = 0.70, p < 0.01). These results suggest that intramuscular hypoxia might facilitate muscular hypertrophy with PRE being more effective than FRE.

Evaluation of Functional Hyperemia Using NIRTRS Without the Influence of Fat Layer Thickness.

Fat layer thickness (FLT) affects near infrared spectroscopy (NIRS) measurement. The aim of this study was to determine an indicator of muscle function with less influence of FLT, even without normalization, by comparing muscle O2 dynamics during exercise in subjects with similar physical characteristics except for FLT. Healthy male subjects with thick FLT (n = 5, FLT: 5.3 ± 0.4 mm) and those with thin FLT (n = 6, FLT: 3.5 ± 0.5 mm) participated in this study. All subjects performed constant work cycling exercise (CWE) at moderate intensity for 6 min. Oxygenated hemoglobin concentration, deoxygenated hemoglobin concentration and total hemoglobin concentration were monitored by using time resolved NIRS (NIRTRS). VO2peak was not significantly different between THICK and THIN (THICK: 54.0 ± 1.8, THIN: 50.0 ± 6.2 mL/kg/min). Changes in all NIRTRS variables at the onset of CWE were significantly larger in THIN than THICK, and the changes in each variable were significantly correlated to FLT. In contrast, there were no relationships between changes in NIRTRS variables during CWE and FLT. These results suggest that muscle deoxygenation at the onset of exercise, which is used as muscle O2 extraction, can be strongly influenced by FLT. In contrast, muscle oxygenation during CWE, which is used as exercise-induced functional hyperemia , may not be influenced by FLT.

Effects of the Drop-set and Reverse Drop-set Methods on the Muscle Activity and Intramuscular Oxygenation of the Triceps Brachii among Trained and Untrained Individuals.

Influence of different load exercise to muscle activity during subsequent exercise with 75% of one repetition maximum (RM) load among trained and untrained individuals was verified. Resistance-trained men who were involved in resistance training (n = 16) and healthy young men who did not exercise regularly (n = 16) were recruited for this study. Each subject performed bench pressing with a narrow grip exercise using two different training set methods, the drop-set (DS) (3 sets × 2-10 repetitions with 95-75% of 1RM) and the reverse drop-set (RDS) (3 sets × 3-10 repetitions with 55-75% of 1RM). The mean concentric contraction power, root mean square (RMS) of electromyography (EMG), area under the oxygenated hemoglobin (Oxy-Hb) curve, and time constant for muscle oxygen consumption (TcVO2mus) values of the triceps brachii were measured during and after the DS and RDS. The trained group demonstrated significantly higher mean muscle power (242.9 ± 39.6 W vs. 215.8 ± 31.7 W), RMS of EMG (86.4 ± 10.4 % vs. 68.3 ± 9.6 %), and area under the Oxy-Hb curve (38.6 ± 7.4 %• sec vs. 29.3 ± 5.8 %• sec) values during the DS than during the RDS (p < 0.05). However, in the untrained group none of the parameters differed significantly for both the DS and RDS. Furthermore, a negative correlation was detected between the area under the Oxy-Hb curve and muscle thickness (r = -0.51, p < 0.01). Long-term effects of DS on muscle strengthening and hypertrophy will be explored in further research.

Once-weekly muscle endurance and strength training prevents deterioration of muscle oxidative function and attenuates the degree of strength decline during 3-week forearm immobilization.

PURPOSE: Muscle unloading causes muscle function deterioration, but the extent to which training frequency or volume can be reduced while preserving muscle function during muscle unloading is unknown. We examined the effects of low-volume muscle endurance and strength training on forearm muscle oxidative capacity, endurance, and strength during a 3-week immobilization. METHODS: Twenty-seven, healthy, male volunteers were divided into four groups: immobilization only (IMM); immobilization with endurance and strength training, once-weekly (IMM + EST1) or twice-weekly (IMM + EST2); and control, without immobilization or training (CNT). Endurance training involved dynamic handgrip exercise, at 30% of maximal voluntary contraction (MVC), until exhaustion (~60 s). Strength training involved intermittent isometric handgrip exercise at 70% MVC (40 s). Muscle oxidative capacity was evaluated after exercise using the phosphocreatine recovery time constant using (31)phosphorus magnetic resonance spectroscopy. Endurance performance was evaluated according to the total work during dynamic handgrip exercise at 30% MVC at 1 Hz until exhaustion. RESULTS: Muscle oxidative capacity and total work deterioration was restricted to the IMM (P < 0.05) group. MVC decreased in the IMM and IMM + EST1 (P < 0.05) groups. However, the MVC amplitude decrease in the IMM + EST1 group was smaller than that in the IMM (P < 0.05) group. MVC remained unchanged in the other groups. CONCLUSION: During the 3-week immobilization, twice-weekly low-volume muscle endurance and strength training prevented deterioration in muscle strength, oxidative capacity, and endurance performance. Moreover, once-weekly muscle endurance and strength training prevented the deterioration of muscle oxidative capacity and endurance performance, and attenuated the degree of muscle strength decline.

A single dose of oral nattokinase accelerates skin temperature recovery after cold water immersion: A double-blind, placebo-controlled crossover study.

Nattokinase (NK) intake may improve blood flow; however, its effects on skin temperature, which is predominantly controlled by skin surface blood flow, are unknown. The purpose of this study was to determine the effects of a single dose of NK on changes in skin temperature after cold water immersion. A double-blinded, placebo-controlled, crossover intervention study was performed on nine healthy men. The participants were randomised to receive either a single dose of 2,000 fibrinolytic units (FU) of NK or a placebo with subsequent crossover. Two hours after supplementation, the participants immersed both hands in a water bath maintained at 10 °C for 1 min. Skin temperature, perceived coldness, cardiac output, and sympathetic nervous activity were measured before, during, and after water immersion. Two-way analysis of variance showed a significant effect of treatment interaction on the skin temperature of the middle finger, palm, and back of the right hand (p < 0.05). These findings represented that the skin temperatures of the middle finger, palm, and back of the right hand immersed in the cold water were significantly dropped due to the cold water immersion, and then recovered more quickly by NK intake than by placebo intake. The results of the current study highlight the potential implications of NK for the prevention of excessive vasoconstriction. It may be more significant for those with cold-sensitive constitution, such as women and elderly. In contrast, the acute administration of 2,000 FU of NK did not affect changes in heart rate, cardiac output, sympathetic nervous activity compared with a placebo in healthy men.

Effects of Prolonged Sitting with or without Elastic Garments on Limb Volume, Arterial Blood Flow, and Muscle Oxygenation.

PURPOSE: The physiological response induced by acute prolonged sitting is not fully understood. Therefore, we examined the effects of 8-h constant sitting on microcirculation and associated factors in the lower extremity among healthy males. We also evaluated the protective effects of lower-pressure thigh-length elastic compression garments on these parameters. METHODS: Nine healthy males (age, 22.6 ± 1.4 yr; body mass index, 22.4 ± 1.8 kg·m-2) completed the 8-h constant sitting experiment. Following baseline measurements, each subject was randomized to wear a lower-pressure elastic garment on the right or left leg from the inguinal region to the ankle joint, with the noncompressed contralateral leg as a control. Circumferences of the calf and malleolus, extracellular water contents, blood flow and shear rate of the dorsal metatarsal artery, and oxygen dynamics in the gastrocnemius muscles were measured in both extremities before and during 8-h constant sitting. RESULTS: Compared with baseline values, 8-h constant sitting caused enlargement of circumferences (calf, 2.4% ± 0.7%; malleolus, 2.7% ± 1.4%), retention of extracellular water in lower extremity muscles (10.1% ± 1.78%), deterioration of the blood flow (61.4% ± 16.2% of baseline) and shear rate of the dorsal metatarsal artery, and decrease in oxygenated hemoglobin and total hemoglobin levels in the gastrocnemius muscle (P < 0.05, respectively). When subjects wore the lower-pressure thigh-length compression garment, a significant reduction of these effects was observed (P < 0.05, for all). CONCLUSIONS: Prolonged sitting for 8 h induced edema, as well as deterioration of the arterial blood flow, shear rate, and microcirculation in lower limb muscles. Conversely, application of the lower-pressure elastic garment successfully prevented the pathophysiological deterioration associated with prolonged sitting.

Impact of brown adipose tissue vascular density on body adiposity in healthy Japanese infants and children.

Background and Objective: The importance of brown adipose tissue (BAT) is well recognized in healthy infants and children. However, information regarding age-related changes in BAT vascular density (BAT-d) and the impact of BAT-d on body adiposity are lacking. This study aimed to evaluate the normal values of BAT-d, factors influencing BAT-d, and the impact of BAT-d on body adiposity in healthy infants and children. Methods: This study included 240 participants (127 girls and 113 boys) aged 1 month to 5 years. The tissue total hemoglobin concentration in the supraclavicular region adjusted according to the subcutaneous adipose tissue thickness (SAT) ([total-Hb-Adj]sup) as BAT-d. SAT in the deltoid and interscapular regions (SATdel+int), the Kaup index (body weight [g]/height or length [cm]/height or length [cm] × 10) as body adiposity, and fertilization season were also measured. Results: The [total-Hb-Adj]sup of boys was higher than that of girls (r = 0.277, p = 0.009). Younger children had a significantly higher Kaup index (r = 0.495, p < 0.001) and SATdel+int (r = 0.614, p < 0.001) than older children. Children who had higher [total-Hb-Adj]sup had a significantly lower Kaup index (r = 0.495, p = 0.037) and SATdel+int (r = 0.614, p < 0.001). Conclusion: The [total-Hb-Adj]sup, as a parameter of BAT-d, is negatively correlated with body adiposity in children aged 1 month to 5 years, and BAT might affect human obesity to a much greater extent than expected. To prevent or treat obesity in early childhood, the level of BAT-d should be considered when using a dietary intervention.

The Effects of 10-Week Strength Training in the Winter on Brown-like Adipose Tissue Vascular Density.

There is no evidence of the effect of exercise training on human brown-like adipose tissue vascular density (BAT-d). Here, we report whether whole-body strength training (ST) in a cold environment increased BAT-d. The participants were 18 men aged 20-31 years. They were randomly assigned to two groups: one that performed ST twice a week at 75% intensity of one-repetition maximum for 10 weeks during winter (EX; n = 9) and a control group that did not perform ST (CT; n = 9). The total hemoglobin concentration in the supraclavicular region determined by time-resolved near-infrared spectroscopy was used as a parameter of BAT-d. ST volume (Tvol) was defined as the mean of the weight × repetition × sets of seven training movements. The number of occasions where the room temperature was lower than the median (NRcold) was counted as an index of potential cold exposure during ST. There was no significant between-group difference in BAT-d. Multiple regression analysis using body mass index, body fat percentage, NRcold, and Tvol as independent variables revealed that NRcold and Tvol were determined as predictive of changes in BAT-d. An appropriate combination of ST with cold environments could be an effective strategy for modulating BAT.

Changes in Optical Path Length Reveal Significant Potential Errors of Muscle Oxygenation Evaluation during Exercise in Humans.

PURPOSE: Near-infrared spectroscopy (NIRS), performed with a commonly available noninvasive tissue oxygenation monitoring device, is based on the modified Beer-Lambert law (MBLL). Although NIRS based on MBLL (NIRSMBLL) assumes that the optical path length (PL) is constant, the effects of changes in PL during exercise on muscle oxygenation calculated by MBLL are still incompletely understood. Thus, the purposes of this study were to examine the changes in optical properties during ramp incremental exercise and to compare muscle oxygen dynamics measured by time-resolved NIRS with those calculated based on MBLL. METHODS: Twenty-two healthy young men performed ramp incremental cycling exercise until exhaustion. Optical properties (reduced scattering coefficient and PL) and absolute oxygenated, deoxygenated, and total hemoglobin and myoglobin concentrations (oxy[Hb + Mb], deoxy[Hb + Mb], and total[Hb + Mb], respectively) at the vastus lateralis were continuously monitored by a three-wavelength (763, 801, and 836) time-resolved NIRS device. The values of oxy-, deoxy-, and total[Hb + Mb] were then recalculated by assuming constant PL. RESULTS: PL at all wavelengths statistically significantly shortened during exercise. In particular, PL at 763 nm was greatly shortened, and the average changes during exercise were a 9.8% ± 3.1% reduction. In addition, significant differences in the kinetics of oxy-, deoxy-, and total[Hb + Mb] between directly measuring PL and assuming constant PL were found. The average changes in measured PL and assuming constant PL-deoxy[Hb + Mb] were increases of 28.8 ± 16.0 µM and increases of 16.4 ± 9.3 µM, respectively. CONCLUSION: Assuming constant PL in NIRSMBLL significantly underestimated actual muscle oxy/deoxygenation as compared with measurements obtained by real-time PL determination. The percent degree of the underestimated oxy/deoxygenation was greater than the percent degree of the changes in PL.

Effects of valproate, an HDAC inhibitor, on the expression of folate carriers and folate metabolism-related genes in the placenta of rats.

Valproate (VPA), an antiepileptic drug, is known to inhibit histone deacetylases (HDACs). Exposure to VPA during pregnancy increases several fetal risks. The maintenance of folate level during pregnancy is essential for adequate fetal development, and the placenta plays a critical role in supplying nutrients to the fetus. The aim of this study was to elucidate the effects of VPA on the gene expression of folate carriers and metabolizing enzymes in the rat placenta at both mid and late gestation periods. Pregnant rats were orally administered VPA on a single day or 4 days (repeated administration). Gene expression of folate carriers (Folr1, Slc19a1, Slc46a1) and metabolizing enzymes (Cth, Mtr, Mtrr, Mthfr, Dhfr) was assessed in the placenta on gestational day (GD) 13 or GD20. In the control rats, the expression of Folr1, Slc46a1, Cth, and Mthfr tended to be upregulated, whereas that of Mtrr and Dhfr was downregulated during gestation; the expression of Slc19a1 and Mtr did not change. Repeated VPA administration reduced the placental expression of Folr1and Mtr on GD20 and increased the expression of Dhfr on GD13 compared with the control. These findings indicate that administration of VPA alters the placental gene expression of folate carriers and metabolism-related enzymes.

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans.

This study examined the relationship between plasma amino acid (AA) concentrations, including branched-chain AAs, and brown adipose tissue density (BAT-d). One hundred and seventy-three subjects (69 men, 104 women) aged 22-68 years were recruited during the winter season. AAs were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. The total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, was assessed using near-infrared time-resolved spectroscopy. Anthropometric parameters, including age, percentage of body fat, and visceral fat, were evaluated. Factors associated with higher (≥74 µM) or lower (<74 µM) [total-Hb]sup were investigated by multiple logistic regression models that included AA concentrations alone (model 1) or AA concentrations and anthropometric parameters (model 2) as independent variables. When adjusted for the false discovery rate, [total-Hb]sup was positively correlated with glycine and asparagine levels in men and with the serine level in both men and women and was negatively correlated with the branched-chain AA concentration in men. Models 1 and 2 correlated with higher or lower BAT-d for men (r = 0.73, p = 0.015) and women (r = 0.58, p = 0.079) and for men (r = 0.82, p = 0.0070) and women (r = 0.70, p = 0.020), respectively. A combination of anthropometric parameters and plasma AA concentrations could be a reliable biomarker for higher and lower BAT-d.

Intra-arterial iodinated radiographic contrast material injection administration in a rat middle cerebral artery occlusion and reperfusion model: possible effects on intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Observations in human interventional stroke treatment led us to hypothesize that iodinated radiographic contrast material use may contribute to intracerebral hemorrhage. Effects of intra-arterial iodinated radiographic contrast material on hemorrhagic transformation after middle cerebral artery occlusion and reperfusion were studied in a placebo-controlled, blinded preclinical study in rats. METHODS: Four groups of male Sprague-Dawley rats were studied: saline group (n=8), contrast group (n=12), heparin group (n=9), and contrast+heparin group (n=9). The middle cerebral artery was occluded for 5 hours using suture placement. Heparin was infused before suture removal and reperfusion. Saline and/or contrast were infused immediately during reperfusion. Incidence, location, and size of hemorrhage were determined by brain necropsy inspection at 24 hours. RESULTS: There was a significant increase in incidence of cortical hemorrhage from control (37.5%), contrast (75.0%), heparin (77.8%) to contrast+heparin (100%; Cochran-Mantel-Haenszel correlation, P<0.01). Both pooled contrast groups (85.7%) and pooled heparin groups (88.9%) had higher rates of cortical intracerebral hemorrhage compared with the control group (P<0.05). Similar trends for increased cortical intracerebral hemorrhage were seen in the contrast-only (P=0.18) and heparin-only (P=0.18) groups. There was a trend for decreased infarct edema in rats receiving contrast versus those without (P=0.06). CONCLUSIONS: Intraarterial iodinated radiographic contrast material may increase cortical intracerebral hemorrhage, similar to heparin. Iodinated radiographic contrast material effect may be additive to heparin effect on the incidence of cortical intracerebral hemorrhage.