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.

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.

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.

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.

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 Capsinoid Intake on Brown Adipose Tissue Vascular Density and Resting Energy Expenditure in Healthy, Middle-Aged Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Capsinoids are some of the most promising ingredients to increase energy expenditure (EE) due to brown adipose tissue (BAT) activation. However, there is limited information regarding the effect of prolonged capsinoid ingestion (CI) on BAT activity and resting EE (REE) in healthy, middle-aged, normal to overweight subjects (Subhealthy) with distinct BAT characteristics. We examined the changes in BAT density (BAT-d), using near-infrared time-resolved spectroscopy, and REE/kg induced by daily CI. Forty Subhealthy [age, 43.8 (mean) years; BMI, 25.4 kg/m2] received either capsinoid (9 mg/day) or a placebo daily for 6 weeks in a double-blind design. Total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, and REE/kg were measured. The changes in post-intervention [total-Hb]sup were greater in the capsinoid group (CA-G) than in the placebo group (PL-G) [5.8 µM (+12.4%) versus 1.0 µM (+2.1%); p = 0.017]. There was a significant relationship between BAT-d and REE/kg; however, post-supplementation REE/kg was not significantly different between the two groups (p = 0.228). In the overweight subgroup, changes in REE/kg were greater in the CA-G than in the PL-G [0.6 cal/kg/min (+4.3%) versus -0.3 cal/kg/min (-2.1%); p = 0.021]. CI enhanced [total-Hb]sup, a reflection of BAT-d, showing a good correlation with REE in Subhealthy.

Near-Infrared Time-Resolved Spectroscopy for Assessing Brown Adipose Tissue Density in Humans: A Review.

Brown adipose tissue (BAT) mediates adaptive thermogenesis upon food intake and cold exposure, thus potentially contributing to the prevention of lifestyle-related diseases. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) with computed tomography (CT) (18FDG-PET/CT) is a standard method for assessing BAT activity and volume in humans. 18FDG-PET/CT has several limitations, including high device cost and ionizing radiation and acute cold exposure necessary to maximally stimulate BAT activity. In contrast, near-infrared spectroscopy (NIRS) has been used for measuring changes in O2-dependent light absorption in the tissue in a non-invasive manner, without using radiation. Among NIRS, time-resolved NIRS (NIRTRS) can quantify the concentrations of oxygenated and deoxygenated hemoglobin ([oxy-Hb] and [deoxy-Hb], respectively) by emitting ultrashort (100 ps) light pulses and counts photons, which are scattered and absorbed in the tissue. The basis for assessing BAT density (BAT-d) using NIRTRS is that the vascular density in the supraclavicular region, as estimated using Hb concentration, is higher in BAT than in white adipose tissue. In contrast, relatively low-cost continuous wavelength NIRS (NIRCWS) is employed for measuring relative changes in oxygenation in tissues. In this review, we provide evidence for the validity of NIRTRS and NIRCWS in estimating human BAT characteristics. The indicators (IndNIRS) examined were [oxy-Hb]sup, [deoxy-Hb]sup, total hemoglobin [total-Hb]sup, Hb O2 saturation (StO2sup), and reduced scattering coefficient ( µs sup' ) in the supraclavicular region, as determined by NIRTRS, and relative changes in corresponding parameters, as determined by NIRCWS. The evidence comprises the relationships between the IndNIRS investigated and those determined by 18FDG-PET/CT; the correlation between the IndNIRS and cold-induced thermogenesis; the relationship of the IndNIRS to parameters measured by 18FDG-PET/CT, which responded to seasonal temperature fluctuations; the relationship of the IndNIRS and plasma lipid metabolites; the analogy of the IndNIRS to chronological and anthropometric data; and changes in the IndNIRS following thermogenic food supplementation. The [total-Hb]sup and [oxy-Hb]sup determined by NIRTRS, but not parameters determined by NIRCWS, exhibited significant correlations with cold-induced thermogenesis parameters and plasma androgens in men in winter or analogies to 18FDG-PET. We conclude that NIRTRS can provide useful information for assessing BAT-d in a simple, rapid, non-invasive way, although further validation study is still needed.

Vigorous-Intensity Physical Activities Are Associated with High Brown Adipose Tissue Density in Humans.

Brown adipose tissue (BAT) plays a role in adaptive thermogenesis in response to cold environments and dietary intake via sympathetic nervous system (SNS) activation. It is unclear whether physical activity increases BAT density (BAT-d). Two-hundred ninety-eight participants (age: 41.2 ± 12.1 (mean ± standard deviation), height: 163.6 ± 8.3 cm, weight: 60.2 ± 11.0 kg, body mass index (BMI): 22.4 ± 3.0 kg/m2, body fat percentage: 25.4 ± 7.5%) without smoking habits were categorized based on their physical activity levels (a group performing physical activities including walking and moderate physical activity (WM) and a group performing WM + vigorous-intensity physical activities (VWM)). We measured the total hemoglobin concentration ([Total-Hb]) in the supraclavicular region, an index of BAT-d, and anthropometric parameters. [Total-Hb] was significantly higher in VWM than WM for all participant groups presumably owing to SNS activation during vigorous-intensity physical activities, and unrelated to the amount of total physical activity levels. Furthermore, multiple regression analysis revealed that BAT-d was related to visceral fat area and VWM in men and related to body fat percentage in women. We conclude that vigorous-intensity physical activities are associated with high BAT-d in humans, especially in men.

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.

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.

Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range.

F18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) along with computed tomography (CT) is a standard method for assessing brown adipose tissue (BAT) activity. We tested the usefulness of near-infrared time-resolved spectroscopy (NIRTRS) as a simple and noninvasive method for evaluating BAT density (BAT-d) by examining the effects of some factors known to influence BAT activity. The total hemoglobin concentration as a parameter of BAT-d was evaluated using NIRTRS in the supraclavicular region in 413 Japanese individuals. The associations were analyzed between BAT-d and sex, age, the percentages of body fat (%BF), visceral fat (VF), and the seasonal ambient temperature (AmT) fluctuations. Age was associated with decreased BAT-d (P < 0.05). There was no sex difference in the BAT-d, except for those in their twenties. Multivariate analyses revealed that %BF and VF were correlated with BAT-d, and the lower AmT (around 4°C or 5°C) for 4 and 6 weeks prior to the measurement day was associated with an increase in the BAT-d. Our NIRTRS results were analogous to those reported with FDG18-PET / CT, indicating the usefulness of NIRTRS. BAT-d might increase during the 4 and 6 weeks after the AmT decreases to lower than 4°C or 5°C.

The Effects of Passive Cycling Exercise for 20 min on Cardiorespiratory Dynamics in Healthy Men [corrected].

An increase in the incidence rate of cardiovascular disease is attributed to high daily sitting time, while a drop in risk of cardiovascular disease comes from a decrease in daily sitting time, rather than an increase in physical activity levels. Although short-duration passive exercise increases energy expenditure and blood flow, few studies have reported on the responses of cardiorespiratory dynamics to long-duration passive exercise. The purpose of this study was to consider the effect of long-duration passive exercise for 20 min on cardiorespiratory and muscle oxygen dynamics. Eight healthy men continuously performed passive exercise using a cycle ergometer for 20 min at 50 rpm. Changes in oxygen uptake, cardiac output and muscle oxygenation were measured during passive cycling exercise. The oxygen uptake at 1 min after the start of passive exercise was significantly increased, compared to resting level, but subsequently returned to the same as resting level. Cardiac output showed no change during passive cycling exercise. Tissue oxygen saturation increased after the start of passive exercise and subsequently maintained steady state. These results suggest that the effect of increases in energy expenditure was not maintained by passive exercise for 20 min. In addition, it is likely that passive cycling exercise for 20 min has an effect on peripheral circulation, although the exercise seems to have no effect on central circulation.

Muscle Deoxygenation and Its Heterogeneity Changes After Endurance Training.

The purpose of this study was to elucidate the time course of muscle deoxygenation and its heterogeneity changes through endurance training. Nine healthy untrained male participated in this study. The subjects performed a ramp incremental cycle exercise protocol to estimate VO2peak and muscle tissue oxygen saturation (SmO2) distribution in the VL muscle before and after 3 (3 wk-T) and 6 weeks of endurance training (6 wk-T). The probe of multi-channel near infrared spatially resolved spectroscopy was attached to the left vastus lateralis muscle along the direction of the long axis. The subjects performed cycle exercise at 60 % of VO2peak for 30 min/day, 3 days/week as the endurance training. After the training, VO2peak at 3 wk-T and 6 wk-T were significantly increased compared to pre-training (Pre-T) and VO2peak at 6 wk-T was significantly increased compared to 3 wk-T. Mean SmO2 within measurement sites at VO2peak was significantly decreased after 3 wk-T and 6 wk-T compared to Pre-T, but mean SmO2 was not significantly different between 3 wk-T and 6 wk-T. Conversely, the heterogeneity of the SmO2 during exercise was not significantly changed through endurance training. A significantly negative correlation was found between ΔVO2 and ΔSmO2 after the first 3 weeks of endurance training. In contrast, no correlation was found betweenΔVO2 and ΔSmO2 after the last 3 weeks of endurance training. These results suggest that the enhanced muscle O2 availability may be one of the primary factors in increasing VO2peak after the first 3 weeks of endurance training.