Additive impact of soy protein dietary intake and exercise on visceral fat mass reduction and mitochondrial complex I activation in skeletal muscle.

Soy protein has shown remarkable effectiveness in reducing fat mass compared with other protein sources, and exercise has the potential to further enhance this fat loss effect. Previous studies have demonstrated that soy protein intake leads to decreased fatty acid synthesis, which contributes to its fat-loss properties. However, the exact mechanism by which these lipids are consumed remains unclear. To investigate this, we conducted a comprehensive study using C57/BL6 male mice, comparing the effects of soy and casein proteins with and without exercise (Casein-Sed, Casein-Ex, Soy-Sed, and Soy-Ex groups) under high- and low-protein conditions (14% or 40% protein). Our findings revealed that combining soy protein intake with exercise significantly reduced epididymal white adipose tissue (eWAT) weight, particularly in the high-protein diet group. Further analysis revealed that exercise increased the expression of lipid oxidation-regulatory proteins, including mitochondrial oxidative phosphorylation protein (OXPHOS) complexes, in the plantaris muscle regardless of the protein source. Although soy protein intake did not directly affect muscle mitochondrial protein expression, the activity of OXPHOS complex I was additively enhanced by exercise and soy protein under the 40% protein condition. Notably, complex I activity inversely correlated with eWAT weight in the soy protein diet group. These results highlight the potential link between improved complex I activity induced by soy protein and fat mass reduction, which emphasizes the promising benefits of combining soy protein with exercise in promoting fat loss.NEW & NOTEWORTHY The findings revealed that soy protein intake combined with exercise resulted in reduced adipose tissue weight compared with that obtained with casein protein intake. Furthermore, the joint impact of exercise and soy protein consumption resulted in enhanced activity of oxidative phosphorylation protein (OXPHOS) complex I in fast-twitch muscles, which appears to be associated with fat mass reduction. These findings elucidate the potential additive effects of soy protein and exercise on body weight management.

Association between oxidative balance score and inflammatory markers in middle-aged and older Japanese people.

PURPOSE: This study aimed to investigate the association between oxidative balance score (OBS), wherein higher OBSs indicate lower oxidative stress, and high-sensitivity C-reactive protein (hs-CRP), as well as inflammatory scores, in a large cohort of Japanese adults. METHODS: In total, 9703 individuals aged 40-69 years participated in a baseline survey of a population-based cohort study in Saga, Japan (2005-2007). OBSs were calculated from 11 prooxidant and antioxidant lifestyle factors, including dietary intake, physical activity, alcohol consumption, and smoking status. Lifestyle data, including dietary intake, were obtained using a self-administered questionnaire. Adjusted geometric means of serum hs-CRP levels were calculated based on OBS quartiles, and linear trend tests were performed, with adjustments for potential confounders. In addition, an inflammatory cytokine z-score was constructed and assessed alongside individual markers. RESULTS: After adjusting for multiple confounders in both sexes, the results showed a significant inverse association between OBS and serum hs-CRP levels in both men and women. These results remained unaltered when the OBS evaluation excluded powerful prooxidants, serum ferritin, or smoking. There was also an association between OBS and lower inflammatory z-score, indicating reduced overall systemic inflammation. CONCLUSIONS: These findings suggest that a higher OBS, indicating a greater predominance of antioxidants over prooxidant exposure, is associated with lower hs-CRP levels and reduced systemic inflammation, regardless of sex.

Evaluation of protein requirements using the indicator amino acid oxidation method: a scoping review.

BACKGROUND: The indicator amino acid oxidation (IAAO) method has been accepted as an approach to evaluate habitual protein requirements under free-living conditions. OBJECTIVES: This scoping review reports on literature that evaluated protein requirements in humans using the IAAO methods. METHODS: Three databases (PubMed/Medline, Web of Science, and ProQuest) were systematically searched to identify studies that evaluated protein requirements using the IAAO method published in English until 5 June, 2023. We evaluated the study quality using previously developed criteria. We extracted the characteristics of the study design and the results of protein requirements. Two reviewers conducted both reviews and quality assessments independently; any differences among them were resolved by consensus or agreement of all team members. RESULTS: We extracted 16 articles targeting children, young adults (including pregnant women, resistance training athletes, endurance-training athletes, and team sports), and older adults. In quality assessment, 14 studies were evaluated "strong," but the remaining 2 were "moderate." These studies were conducted in only 3 countries and did not include all sexes or life stages. The range of the estimated average protein requirements of each life stage was 1.30 g/kg body weight/d for children, 0.87 to 2.10 (0.87-0.93 for general young adults, 1.22-1.52 for pregnant women, 1.49-2.00 for resistance-trained athletes, 1.65-2.10 for endurance athletes, and 1.20-1.41 for team sports athletes) g/kg body weight/d for young adults, and 0.85 to 0.96 g/kg body weight/d for older adults. CONCLUSIONS: Protein requirements in 14 studies were higher than the current reference for each sex, life stage, and physical activity that are related to protein requirements. In the future, protein requirements of various populations including sex and life stage could be assessed using the IAAO methods worldwide.

Delayed Eating Schedule Raises Mean Glucose Levels in Young Adult Males: a Randomized Controlled Cross-Over Trial.

BACKGROUND: Misalignment of meals to the biological clock may cause adverse effects on glucose metabolism. However, the effects of repeated different eating schedules (early compared with late) on glucose concentration throughout the day are poorly understood. OBJECTIVES: We examined the effects of different eating schedules on the 24-h glucose response using a continuous glucose monitor (CGM). METHODS: Eight young adult males (age, 20.9 ± 3.4 y; body mass index: 21.3 ± 1.8 kg/m2) each followed 2 different eating schedules (early [08:30, 13:30, and 19:30] and late [12:00, 17:00, and 23:00]) in random order. These diet interventions were conducted for 8 d, with an experimental period of 3 d and 2 nights (from dinner on day 7) after 7 d of free living. The 3 meals in each intervention were nutritionally equivalent (55% carbohydrate, 15% protein, and 30% fat). The 24-h mean interstitial glucose concentration on day 8 was obtained under controlled conditions using the CGM (primary outcome). These concentrations were compared among the following 3 schedules using Dunnett's test, with the early eating schedule as reference (1 compared with 2 and 1 compared with 3): 1) early eating schedule (control), 2) late eating schedule according to the clock time (08:00 on day 8 to 08:00 on day 9), and 3) late eating schedule according to the time elapsed since the first meal for 24 h. RESULTS: The 24-h mean ± SD interstitial glucose concentrations when participants followed the late eating schedule were higher than those when they followed the early eating schedule in terms of clock time (91.2 ± 2.9 compared with 99.2 ± 4.6 mg/dL, P = 0.003) and time elapsed (91.2 ± 2.9 compared with 98.3 ± 3.8 mg/dL, P < 0.001). CONCLUSIONS: A late eating schedule increases the mean 24-h interstitial glucose concentration in young adult males. This insight will have useful implications in determining meal timings, especially for those with conditions such as diabetes.

Comparison of Bioelectrical Impedance Indices for Skeletal Muscle Mass and Intracellular Water Measurements of Physically Active Young Men and Athletes.

BACKGROUND: Bioelectrical impedance analysis (BIA) is a minimally invasive, safe, easy, and quick technology used to determine body composition. OBJECTIVES: We compared the relationship among impedance indices obtained using single-frequency BIA, multi-frequency BIA, bioelectrical impedance spectroscopy (BIS), and skeletal muscle mass (SMM) of physically active young men and athletes using the creatine (methyl-d3) dilution method. We also compared the SMM and intracellular water (ICW) of athletes and active young men measured using a reference stable isotope dilution and BIS method, respectively. METHODS: We analyzed data from 28 men (mean age, 20 ± 2 y) who exercised regularly. Single-frequency BIA at 5 kHz and 50 kHz (R5 and R50), multi-frequency BIA (R250-5), and BIS (RICW) methods of determining the SMM were compared. The deuterium and sodium bromide dilution methods of obtaining the total body water, ICW, and extracellular water measurements were also used, and the results were compared to those acquired using bioimpedance methods. RESULTS: The correlation coefficients between SMM and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.738, 0.762, 0.790, and 0.790, respectively (P < 0.01). The correlation coefficients between ICW and L2/R5, L2/R50, L2/R250-5, and L2/RICW were 0.660, 0.687, 0.758, and 0.730, respectively (P < 0.001). However, the correlation coefficients of L2/R50, L2/R250-5, and L2/RICW for SMM and ICW were not significantly different. CONCLUSIONS: Our findings suggest that single-frequency BIA at L2/R50, multi-frequency BIA, and BIS are valid for assessing the SMM of athletes and active young men. Additionally, we confirmed that the SMM and ICW were correlated with single-frequency BIA, multi-frequency BIA, and BIS. Bioimpedance technologies may be dependable and practical means for assessing SMM and hydration compartment status of active young adult males; however, cross-validation is needed.

The neuronal nitric oxide synthase expression increases during satellite cell-derived primary myoblasts differentiation.

The neuronal nitric oxide synthase (nNOS; encoded by NOS1)-derived nitric oxide (NO) plays an important role in maintaining skeletal muscle mass. In adult skeletal muscle, nNOS localizes to the cell membrane, cytosol, and nucleus, and regulates muscle hypertrophy and atrophy in various subcellular fractions. However, its role in muscle stem cells (also known as muscle satellite cells), which provide myonuclei for postnatal muscle growth, maintenance, and regeneration, remains unclear. The present study aimed to determine nNOS expression in muscle satellite cell-derived primary myoblasts during differentiation and its DNA methylation levels, an epigenetic modification that controls gene expression. Undifferentiated and differentiated satellite cell-derived primary myoblasts were found to express nNOS. Immunohistochemical analysis revealed that nNOS colocalized with Pax7 (satellite cell marker) only in the undifferentiated myoblasts. Furthermore, nNOS immunoreactivity spread to the cytosol of Pax7-negative differentiated myotube-like cells. The level of Nos1µ mRNA, the main isoform of skeletal muscle nNOS, was increased in differentiated satellite cell-derived primary myoblasts compared to that in the undifferentiated cells. However, Nos1 methylation levels remained unchanged during differentiation. These findings suggest that nNOS induction and the appropriate transition of its subcellular localization may contribute to muscle differentiation.

Moderate-to-vigorous Physical Activity and Sedentary Behavior Are Independently Associated With Renal Function: A Cross-sectional Study.

BACKGROUND: Little is known about whether insufficient moderate-to-vigorous physical activity (MVPA) and longer sedentary behavior (SB) are independently associated with estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), whether they interact with known risk factors for CKD, and the effect of replacing sedentary time with an equivalent duration of physical activity on kidney function. METHODS: We examined the cross-sectional association of MVPA and SB with eGFR and CKD in 66,603 Japanese cohort study in 14 areas from 2004 to 2013. MVPA and SB were estimated using a self-reported questionnaire, and CKD was defined as eGFR <60 mL/min/1.73 m2. Multiple linear regression analyses, logistic regression analyses, and an isotemporal substitution model were applied. RESULTS: After adjusting for potential confounders, higher MVPA and longer SB were independently associated with higher eGFR (P for trend MVPA <0.0001) and lower eGFR (P for trend SB <0.0001), and a lower odds ratio (OR) of CKD (adjusted OR of MVPA ≥20 MET·h/day, 0.76; 95% confidence interval [CI], 0.68-0.85 compared to MVPA <5 MET·h/day) and a higher OR of CKD (adjusted OR of SB ≥16 h/day, 1.81; 95% CI, 1.52-2.15 compared to SB <7 h/day), respectively. The negative association between MVPA and CKD was stronger in men, and significant interactions between sex and MVPA were detected. Replacing 1 hour of SB with 1 hour of physical activity was associated with about 3 to 4% lower OR of CKD. CONCLUSION: These findings indicate that replacing SB with physical activity may benefit kidney function, especially in men, adding to the possible evidence on CKD prevention.

The differences in renal hemodynamic response following high-intensity exercise between younger and older males.

BACKGROUND: Renal blood flow (RBF) decreases with exercise, but this change is only temporary, and habitual exercise may be an effective method to improve renal function. The kidney shows structural and functional changes with aging, but it is unclear how aging affects the hemodynamic response of the kidneys to exercise. Therefore, we evaluated the differences in the hemodynamic response of the kidneys to high-intensity exercise between younger and older men. METHODS: Sixteen men (8 young and 8 older) underwent an incremental exercise test using a cycle ergometer with a 1-min warm up followed by exercise at 10-20 W/min until the discontinuation criteria were met. Renal hemodynamics were assessed before exercise, immediately after exercise, and at 60-min after exercise using ultrasound echo. RESULTS: High-intensity exercise significantly reduced RBF in both groups (younger: ∆ - 53 ± 16%, p = 0.0005; older: ∆ - 53 ± 19%, p = 0.0004). In the younger group, RBF returned to the pre-exercise level 60-min after exercise (∆ - 0.4 ± 5.7%, p > 0.9999). In contrast, RBF 60-min after exercise was significantly lower than that before exercise in the older group (∆ - 24 ± 19%, p = 0.0006). The older group had significantly lower RBF than younger adults 60-min after exercise (423 ± 32 vs. 301 ± 98 mL/min, p = 0.0283). CONCLUSIONS: Our findings demonstrate that RBF following high-intensity exercise recovered 60-min after exercise in younger group, whereas RBF recovery was delayed in the older group.

The Validity of Ultra-Short-Term Heart Rate Variability during Cycling Exercise.

Ultra-short-term heart rate variability (HRV) has been validated in the resting state, but its validity during exercise is unclear. This study aimed to examine the validity in ultra-short-term HRV during exercise considering the different exercise intensities. HRVs of twenty-nine healthy adults were measured during incremental cycle exercise tests. HRV parameters (Time-, frequency-domain and non-linear) corresponding to each of the 20% (low), 50% (moderate), and 80% (high) peak oxygen uptakes were compared between the different time segments of HRV analysis (180 s (sec) segment vs. 30, 60, 90, and 120-sec segments). Overall, the differences (bias) between ultra-short-term HRVs increased as the time segment became shorter. In moderate- and high-intensity exercises, the differences in ultra-short-term HRV were more significant than in low intensity exercise. Thus, we discovered that the validity of ultra-short-term HRV differed with the duration of the time segment and exercise intensities. However, the ultra-short-term HRV is feasible in the cycling exercise, and we determined some optimal time duration for HRV analysis for across exercise intensities during the incremental cycling exercise.

Short-term running exercise alters DNA methylation patterns in neuronal nitric oxide synthase and brain-derived neurotrophic factor genes in the mouse hippocampus and reduces anxiety-like behaviors.

Running exercise has beneficial effects on brain health. However, the effects of relatively short-term running exercise (STEx) on behavior, and its underlying signaling pathways, are poorly understood. In this study, we evaluated the possibility that the regulation by STEx of brain-derived neurotrophic factor (BDNF) and neuronal nitric oxide synthase (nNOS, encoded by NOS1), which are important molecules for anxiety regulation, might involve mechanisms of epigenetic modification, such as DNA methylation. C57BL/6J male mice were divided into sedentary (SED, n = 12) and STEx (EX, n = 15) groups; STEx was conducted with the mice for a duration of 11 days. STEx reduced anxiety-like behaviors, and STEx reduced Nos1α and increased Bdnf exon I and IV mRNA levels in the hippocampus. Interestingly, behavioral parameters were associated with Bdnf exon I and IV and Nos1α mRNA levels in the ventral, but not dorsal, hippocampal region. However, STEx had no effect on peroxisome proliferator-activated receptor-γ coactivator 1α (Pgc-1α) or fibronectin type III domain-containing 5 (Fndc5) mRNA levels, which are relatively long-term exercise-induced upstream regulators of BDNF. In parallel with gene expression changes, we found, for the first time, that STEx downregulated Bdnf promoter IV and upregulated Nos1 DNA methylation levels in the hippocampus, and these patterns were partially different between the dorsal and ventral regions. These findings suggest that the beneficial effects of running exercise on mood regulation may be controlled by alterations in epigenetic mechanisms, especially in the ventral hippocampus. These effects occur even after a relatively short-term period of exercise.

The effects of breaking sedentary time with different intensity exercise bouts on energy metabolism: A randomized cross-over controlled trial.

BACKGROUND AND AIMS: Breaking up sedentary periods, particularly with light activity, increases total energy expenditure (EE), and helps provide better glycemic control. However, the effects of activities of various intensities to interrupt prolonged sedentary time are unclear. The purpose of the present study was to examine potential differences in glycemic control and EE from breaking up sedentary time with short exercise bouts of different intensities. METHODS AND RESULTS: Nine overweight/obesity young men underwent whole body indirect calorimetry at 19:00 on day 1 and stayed overnight. After awakening on day 2, they performed short duration jogging every 30 min over 8 h (16-time bouts in total) under 3 different conditions with the same running distance: (1) lactate threshold (LT) for 2 min, (2) 60% LT for 200 s, and (3) onset of blood lactate accumulation (OBLA) for 75 s. The 24-h EE and interstitial glucose concentration (from 8:00 to 19:00 on day 2) was continuously measured throughout the trials. The standard deviation during intervention and indexes of postprandial of the interstitial glucose concentration was significantly lower at LT and OBLA than at 60% LT (p < 0.05). The 24-h EE was not significantly different among conditions, but EE at OBLA during intervention was slightly but significantly higher than at 60% LT and LT. CONCLUSION: Breaking up sedentary time with short-duration jogging at LT and with OBLA intensities may have better glycemic control and increased use of carbohydrate as a fuel, while short-duration a jogging at OBLA intensity may increase EE. TRIAL REGISTRATION: UMIN000041361.

Association between the inability to identify particular odors and physical performance, cognitive function, and/or brain atrophy in community-dwelling older adults from the Fukuoka Island City study.

BACKGROUND: Olfactory dysfunction is associated with severe brain atrophy and cognitive impairment in Parkinson's disease. However, it remains unknown whether an inability to identify particular odors is associated with physical performance, cognitive function, and/or brain atrophy in community-dwelling older adults. METHODS: In this cross-sectional study, 44 community-dwelling older adults were included (14 males, 30 females; mean age: 72.4 ± 5.7 years, range: 63-85 years). The Odor Stick Identification Test for Japanese, consisting of 12 odors, was used to examine olfaction. Subjects also completed physical performance (lower limb function, balance, and gait speed) and cognitive function (global cognition, logical memory, and the Trail Making Tests). Additionally, magnetic resonance imaging was used to investigate brain atrophy in the bilateral medial temporal area (MTA) and whole gray matter using the voxel-based specific regional analysis system for Alzheimer's disease. RESULTS: Total olfaction was not significantly associated with physical performance, cognitive function, or brain atrophy. However, MTA atrophy was associated with an inability to identify Japanese orange (B: - 0.293; ß: - 0.347; p < .05) after adjusting for age and sex (R2: 0.328; adjusted R2: 0.277). Subjects who were unable to identify Japanese orange (n = 30) had worse MTA atrophy than those who were able to identify Japanese orange (n = 14), even after adjusting for covariates (p < .05). CONCLUSIONS: Total olfaction was not associated with physical performance, cognitive function, or brain atrophy. However, an inability to identify Japanese orange odor was independently associated with mild MTA atrophy among community-dwelling older adults.

The interactive effects of acute exercise and hypoxia on cognitive performance: A narrative review.

Acute moderate intensity exercise has been shown to improve cognitive performance. In contrast, hypoxia is believed to impair cognitive performance. The detrimental effects of hypoxia on cognitive performance are primarily dependent on the severity and duration of exposure. In this review, we describe how acute exercise under hypoxia alters cognitive performance, and propose that the combined effects of acute exercise and hypoxia on cognitive performance are mainly determined by interaction among exercise intensity and duration, the severity of hypoxia, and duration of exposure to hypoxia. We discuss the physiological mechanism(s) of the interaction and suggest that alterations in neurotransmitter function, cerebral blood flow, and possibly cerebral metabolism are the primary candidates that determine cognitive performance when acute exercise is combined with hypoxia. Furthermore, acclimatization appears to counteract impaired cognitive performance during prolonged exposure to hypoxia although the precise physiological mechanism(s) responsible for this amelioration remain to be elucidated. This review has implications for sporting, occupational, and recreational activities at terrestrial high altitude where cognitive performance is essential. Further studies are required to understand physiological mechanisms that determine cognitive performance when acute exercise is performed in hypoxia.

Evaluation of fat-free mass hydration in athletes and non-athletes.

PURPOSE: To evaluate the hydration of fat-free mass (FFM) in athletes and non-athletes. METHODS: We analyzed the data of 128 healthy young adults (athletes: 61 men, 36 women; non-athletes: 19 men, 12 women) using the two-component (2C), 3C and 4C models. Under-water weighing or air-displacement plethysmography and deuterium dilution methods were used for estimating body density and total body water, respectively. The bone mineral content (BMC) was determined using whole-body scans by dual-energy X-ray absorptiometry. RESULTS: There was no significant difference in FFM hydration between the athletes (men, 72.3 ± 1.3%; women, 71.8 ± 1.3%) and non-athletes (men, 72.1 ± 1.2%; women, 72.2% ± 1.0%) in the 3C model. The total mean FFM hydration (72.1% ± 1.3%) was similar to the corresponding value in the literature (~ 73%). The estimation error of the percentage fat by the 2C vs the 4C model was significantly and highly correlated with hydration (r = 0.96), BMC (r = - 0.70), and total body protein (r = - 0.86) in the 4C model FFM. CONCLUSION: Although FFM hydration was similar in athletes and non-athletes, it would be underestimated or overestimated when the 2C model is used for evaluation, and the biological FFM hydration value deviates from the 73% value inter-individually. Despite that this inter-individual variation in FFM hydration is low in terms of between-individual standard deviation (1.3%), the BMC and total body protein differ greatly in athletes, and when it affects FFM hydration, it may also affect the percentage fat measurement in the 2C model. Thus, FFM hydration would not be affected by FFM, percent body fat, or the athletic status.

[Physical parameters and physical function in older drivers with driving-related anxiety: the Nakagawa Study].

AIM: This study investigated whether driving-related anxiety was independently associated with physical parameters and physical function in community-dwelling older people. METHODS: Participants were 523 community-dwelling older drivers (353 men and 170 women). Participants self-reported driving-related anxiety when driving in familiar environments, and completed physical assessments: visual impairment, auditory impairment, cerebrovascular disease (CVD), hand grip strength, knee extension strength, timed up and go (TUG), chair stand, one leg standing with open eyes, functional reach, vertical jump, preferred gait speed and maximal gait speed. Participants were divided into a driving-related anxiety group (72.8±5.1 years; 21 men, seven women) and a no-anxiety (non-anxiety) group (70.7±4.7 years; 325 men, 163 women). We examined physical performance differences between the anxiety and non-anxiety groups using analysis of covariance, and investigated the relationship between anxiety, physical function and performance using logistic regression analysis (forward stepwise selection). RESULTS: The driving-related anxiety group was significantly older, with higher rates of visual impairment, auditory impairment, and CVD than the non-anxiety group. The anxiety group exhibited independently poorer TUG and maximal gait speed (P<0.05 for both). Logistic regression analysis revealed significant relationships between anxiety and visual impairment (odds ratio [OR]: 5.6, 95% confidence interval [CI]: 2.5-12.6), auditory impairment (OR: 3.0, 95% CI: 1.3-7.0), TUG (OR: 1.46, 95% CI: 1.1-1.9) and CVD (OR: 3.1, 95% CI: 1.0-9.4) (P<0.05 for all). CONCLUSIONS: Driving-related anxiety was significantly associated with worse physical performance, visual impairment, auditory impairment, and CVD in community-dwelling older drivers.

One week, but not 12 hours, of cast immobilization alters promotor DNA methylation patterns in the nNOS gene in mouse skeletal muscle.

KEY POINTS: DNA methylation may play an important role in regulating gene expression in skeletal muscle to adapt to physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) in skeletal muscle is a key regulator of skeletal muscle mass; however, it is unclear whether nNOS expression is regulated by DNA methylation. We found that 1 week of cast immobilization increased nNOS DNA methylation levels and downregulated nNOS gene expression in atrophic slow-twitch soleus muscle from the mouse leg. These changes were not detected in non-atrophic fast-twitch extensor digitorum longus muscle. Twelve hours of cast immobilization decreased nNOS gene expression, whereas nNOS DNA methylation levels were unchanged, suggesting that downregulation of nNOS gene expression by short-term muscle inactivity is independent of the DNA methylation pattern. These findings contribute to a better understanding of the maintenance of skeletal muscle mass and prevention of muscle atrophy by epigenetic mechanisms via the nNOS/NO pathway. ABSTRACT: DNA methylation is a mechanism that controls gene expression in skeletal muscle under various environmental stimuli, such as physical activity and inactivity. Neuronal nitric oxide synthase (nNOS) regulates muscle atrophy in skeletal muscle. However, the mechanisms regulating nNOS expression in atrophic muscle remain unclear. We hypothesized that nNOS expression in atrophic muscle is regulated by DNA methylation of the nNOS promotor in soleus (Sol; slow-twitch fibre dominant) and extensor digitorum longus (EDL; fast-twitch fibre dominant) muscles. One week of cast immobilization induced significant muscle atrophy in Sol but not in EDL. We showed that 1 week of cast immobilization increased nNOS DNA methylation levels in Sol, although only a minor change was detected in EDL. Consistent with the increased DNA methylation levels in atrophic Sol, the gene expression levels of total nNOS and nNOSµ (i.e. the major splicing variant of nNOS in skeletal muscle) decreased. The abundance of the nNOS protein and cell membrane (especially type IIa fibre) immunoreactivity also decreased in atrophic Sol. These changes were not observed in EDL after 1 week of cast immobilization. Furthermore, despite the lack of significant atrophy, 12 h of cast immobilization decreased gene expression levels of total nNOS and nNOSµ in Sol. However, no association was detected between nNOS DNA methylation and gene expression. The expression of the nNOSß gene, another splicing variant of nNOS, in EDL was unchanged by cast immobilization, whereas its expression was not detected in Sol. We concluded that chronic adaptation of nNOS gene expression in cast immobilized muscle may involve nNOS DNA methylation.

Long-term Body Weight Gain After Maturity is Associated With the Incidence of Chronic Kidney Disease (CKD), Independent of Current Body Weight, in Middle-aged and Older Men.

BACKGROUND: This study investigated the relationship between long-term body weight gain after maturity and the incidence of chronic kidney disease (CKD). METHODS: The participants were 303 men without a history of cardiovascular and cerebrovascular diseases, kidney dysfunction, or dialysis treatment. Their body weight gain after maturity was examined using a standardized self-administered questionnaire. The participants were divided into two groups based on the presence/absence of a body weight gain of ≥10 kg since 20 years of age. RESULTS: After a 6-year follow-up, the cumulative incidence of CKD was significantly higher in participants with a body weight gain of ≥10 kg than in participants without body weight a body weight gain of ≥10 kg since 20 years of age (log-rank test: P = 0.041). After adjusting for the age, body mass index, estimated glomerular filtration rate levels, smoking and drinking habits, and the presence of hypertension, dyslipidemia, and hyperglycemia at baseline, the normal body weight participants with a body weight gain of ≥10 kg since 20 years of age was significantly related to the incidence of CKD (hazard ratio 2.47; 95% confidence of interval, 1.02-6.01, P = 0.045). CONCLUSIONS: These results suggest that long-term body weight gain after maturity in normal body weight participants may be associated with the incidence of CKD, independent of current body weight.

Effect of exercise intensity on renal blood flow in patients with chronic kidney disease stage 2.

BACKGROUND: Acute exercise reduces renal blood flow (RBF). However, the effect of exercise intensity on RBF in patients with chronic kidney disease (CKD) stage 2 is not known. We investigated the association between RBF and exercise intensity in patients with CKD stage 2 using pulsed Doppler ultrasonography. METHODS: Eight men with CKD stage 2 (cystatin C-based estimate of glomerular filtration rate: 60-89 ml/min/1.73 m2) participated in this study. Using a bicycle ergometer, participants undertook a maximal graded exercise test (MGET) (experiment 1) and a multi-stage exercise test (experiment 2) to determine their lactate threshold (LT). Participants undertook a multi-stage exercise test for 4-min each. Workloads of 60%, 80%, 100%, 120%, and 140% of LT were used in experiment 3. RBF was measured by pulsed Doppler ultrasonography at rest, immediately after exercise, and 1 h after exercise in experiment 1, and at rest and immediately after each exercise bout in experiment 3. RESULTS: Renal blood flow after the MGET was 52% lower than at rest, and did not recover as well as after the exercise test. Cross-sectional area (CSA) was significantly lower after graded exercise. RBF tended to be lower at 100% of LT and was significantly lower at 120% of LT. CSA was significantly lower at 100% of LT. CONCLUSIONS: Renal blood flow does not change during exercise until the LT is reached. These findings may assist in making appropriate exercise recommendations to patients with CKD stage 2.

Effects of pain neuroscience education in hospitalized patients with high tibial osteotomy: a quasi-experimental study using propensity score matching.

BACKGROUND: Pain neuroscience education (PNE) has been shown to reduce pain or psychological symptoms in patients with chronic pain and preoperative knee osteoarthritis; however, the evidence of its effectiveness in hospitalized patients who have undergone high tibial osteotomy (HTO) is unknown. This study was performed to determine whether the implementation of a newly developed hospital-time PNE provided by physical therapists to patients after HTO can result in meaningful improvements. METHODS: In total, 119 patients aged ≥45 years with knee osteoarthritis who were scheduled to undergo HTO were analyzed. Patients with a low Pain Catastrophizing Scale (PCS) score of < 21 were excluded. The patients were classified into two groups: those who underwent a combination of PNE and rehabilitation (intervention group, n = 67) and those who underwent rehabilitation only (control group, n = 52). The patients were pseudo-randomized by their baseline demographic factors using a propensity score-matching method. The PNE was based on a psychosocial model and began 1 week postoperatively in a group setting; five 1-h weekly sessions were conducted. The primary outcome was the walking pain score as measured by a numerical rating scale. The secondary outcomes were the pain catastrophizing scores as measured by the PCS, self-efficacy as measured by the Pain Self-Efficacy Questionnaire, and physical function. Measurements were taken at baseline (before surgery) and before discharge from the hospital (5 weeks postoperatively) to identify any intervention effects. RESULTS: After propensity score matching, 52 pairs of patients were extracted. In the intervention group, 46 (88.5%) patients completed the PNE. In total, 44 patients in the intervention group and 52 patients in the control group were analyzed. Five weeks following surgery, the rehabilitation itself had also significantly decreased catastrophizing, and the difference between the two groups had only a small effect size (d = 0.44). CONCLUSIONS: These findings provide preliminary evidence that physical therapist-delivered PNE during hospitalization may help to at least slightly reduce pain catastrophizing in patients with catastrophizing prior to knee arthroplasty. TRIAL REGISTRATION: This trial was retrospectively registered with ClinicalTrials.gov (UMIN000037114) on 19 June 2019.

Habitual Light-intensity Physical Activity and ASC Methylation in a Middle-aged Population.

Apoptosis-associated, speck-like protein containing a caspase recruitment domain (ASC) plays an important role in inflammatory cytokine synthesis in peripheral blood mononuclear cells (PBMCs), and the expression of ASC is suppressed by increased methylation of its CpG sites. The current study investigated the longitudinal association of replacing sedentary time with light-intensity physical activity (LPA) or moderate to vigorous-intensity physical activity (MVPA) on the ASC methylation in middle-aged people. We investigated 1 238 individuals who participated in baseline and 5-year follow-up surveys of a population-based cohort study. Sedentary, LPA and MVPA time were objectively measured using accelerometers. ASC methylation in PBMCs was measured by pyrosequencing. Using a multiple linear regression and employing an isotemporal substitution model, the longitudinal associations of changes in the sedentary time, LPA and MVPA on the changes in the ASC methylation were analyzed after adjusting for potential confounders. Substituting 60 min per day of LPA for sedentary time was associated with 1.17 times (95% confidence interval 1.07, 1.27) higher ASC methylation levels (mean of 7 CpG sites, P<0.001). However, such effects were not seen for MVPA. These results suggest that substituting LPA for sedentary time may be linked with increased (favorable) ASC methylation as a potential biomarker of systemic inflammation.