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The influence of habitual physical activity (PA) on the circulating levels of secreted protein acidic and rich in cysteine (SPARC) remains unclear. The purpose of the current study was to clarify the effects of sedentary time, light-intensity PA (LPA), and moderate- to vigorous-intensity PA (MVPA) on the serum SPARC in a general middle-aged population. The current study is a cross-sectional study of 4,000 men and 6,040 women (40–69 years). Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by enzyme-linked immunosorbent assay. Using an isotemporal substitution model, cross-sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analysed according to sex. Interactions with subject characteristics, such as the body mass index (BMI), smoking, and alcohol consumption, were also examined. In men, replacing 60 min of sedentary time with 60 min of MVPA was significantly associated with 23 ng/mL lower serum SPARC levels (confidence interval: −43, −2) after adjusting for confounders, including the BMI (P = 0.028). A significant interaction between replacing sedentary behaviour with LPA and the BMI on SPARC was detected in women (P = 0.029), although the stratified associations for each BMI level (<25 or ≥25 kg/m2) did not reach significance. The current study suggests that replacing sedentary time with MVPA is associated with reduced serum SPARC levels in middle-aged men, but not in women. In addition, a potential interaction between LPA and the BMI on SPARC was also found in women. Highlights An isotemporal substitution analysis showed that replacing sedentary behaviour with moderate- to vigorous-intensity physical activity (MVPA) is associated with decreased serum SPARC levels in men. Such an inverse association between replacing sedentary behaviour with MVPA and the SPARC levels was not observed in women. A potential interaction between replacing sedentary behaviour with light-intensity PA and the body mass index on the serum SPARC levels was also found in women. [ABSTRACT FROM AUTHOR]

Introduction: Health benefits of physical activity (PA) may be mediated by DNA methylation alterations. The purpose of the current study was to comprehensively identify CpG sites whose methylation levels were associated with accelerometer-assessed total PA in a general Japanese population. Methods: The study participants were from the baseline survey of Saga Japan Multi-institutional Collaborative Cohort. PA was objectively measured by a single-axis accelerometer for 7 d. We used a two-stage strategy. In the discovery stage, we performed a meta-analysis of two epigenome-wide association studies of total PA in 898 individuals (a combination of random sample (n = 507) and case–control study sample (n = 391)). Peripheral blood DNA methylation levels were measured using Infinium EPIC or HM450 arrays. In the replication stage, we subsequently examined whether CpG sites significantly associated (P < 1 × 10−5) with total PA were replicated in another sample (n = 1711), in which methylation levels were measured by pyrosequencing. A multiple linear regression was performed to determine the cross-sectional association between total PA and methylation levels with adjustment for potential confounders, including body mass index. A fixed-effects model was used in the meta-analysis. Correlations between total PA–associated DNA methylation and several inflammatory markers, such as high-sensitivity C-reactive protein, were also conducted. Results: In the meta-analysis, nine CpG sites were significantly associated with total PA (P < 1 × 10−5). Among the nine sites, one site cg07030336 (annotated to VTI1A/ZDHHC6 gene) was successfully replicated (P = 0.009). Conclusions: The current study showed that greater accelerometer-assessed total PA was associated with higher DNA methylation levels at cg07030336 (VTI1A/ZDHHC6) in the general population. In addition, we found a divergent relationship between the methylation levels at cg07030336 and several inflammatory biomarkers. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Studies using self-reported physical activity (PA) showed that higher PA is associated with lower circulating levels of C-reactive protein; in contrast, studies investigating associations of objective PA and other inflammatory markers are limited. We investigated cross-sectional associations of accelerometer-determined PA with circulating levels of myokine-type inflammatory cytokines in a middle-aged Japanese population. Method: A total of 1838 individuals (737 men and 1101 women) aged 40 to 69years participated in the baseline survey of a population-based cohort study in Saga, Japan (2005–2007). Habitual PA was assessed by a single-axis accelerometer. Serum interleukin (IL)-4, IL-6, IL-8, IL-15, and tumor necrosis factor (TNF)-α were measured by a multiplex enzyme-linked immunosorbent assay. Associations between PA and cytokine levels were assessed by multiple regression analysis and analysis of covariance, with adjustment for potential confounders. Results: Step count and PA level (PAL) were inversely associated with TNF-α and IL-15 even after adjusting for BMI. Similarly, greater PA indices were also independently associated with a lower level of inflammatory cytokine z score as an index of overall inflammation. Conclusion: The current results suggest that greater engagement in daily PA may be linked with reduced levels of myokine-type cytokines including IL-15, irrespective of body weight in middle-aged Japanese people. [Copyright &y& Elsevier]

• Rapamycin facilitates autophagic activity in the transected inferior alveolar nerve. • Rapamycin decreases the accumulation of myelin debris attributable to inferior alveolar nerve transection. • Rapamycin promotes axon regeneration of the transected inferior alveolar nerve. Sensory disturbance in the orofacial region owing to trigeminal nerve injury is caused by dental treatment or accident. Commercially available therapeutics are ineffective for the treatment of sensory disturbance. Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Thus, we investigated the therapeutic effects of rapamycin on the sensory disturbance in the mandibular region caused by inferior alveolar nerve (IAN) transection (IANX) in rats. The expression levels of the phosphorylated p70S6K, a downstream molecule of mTOR, in the proximal and distal stumps of the transected IAN were significantly reduced by rapamycin administration to the injured site. Conversely, the increments of both Beclin 1 and microtubule-associated protein-1 light chain 3-II protein levels in the proximal and distal stumps of the transected IAN was induced by rapamycin administration. Immunohistochemical analyses revealed that Beclin 1 was located in Schwann cells in the proximal stump of the IAN. Accumulation of myelin protein zero and myelin basic protein in the proximal and distal stumps of the IAN was significantly reduced by rapamycin administration. Rapamycin administration facilitated axon regeneration after IANX and increased the number of brain-derived neurotrophic factor positive neurons in the trigeminal ganglion. Thus, recovery from sensory disturbance in the lower lip caused by IANX was markedly facilitated by rapamycin. These findings suggest that rapamycin administration is a promising treatment for the sensory disturbance caused by IANX. [ABSTRACT FROM AUTHOR]

• Adiponectin is considered to be beneficial for preventing lifestyle diseases. • Mitochondrial haplogroups have been associated with risks for lifestyle diseases. • Physical activity effect on adiponectin is different between haplogroups M7a and D. Mitochondrial haplogroups F, A, and M7a are associated with increased risks of lifestyle diseases, while haplogroups N9 and D are associated with decreased risks of lifestyle diseases or with longevity. The current study determined the existence of interactions between 5 selected haplogroups and physical activity (PA) on total and high-molecular-weight (HMW) adiponectin in 3,994 men and 6,014 women. The interactions between haplogroups (M7a/D) and PA on adiponectin were significant in men (total and HMW: P -interaction = 0.041 and 0.011). The positive association of PA with adiponectin in men carrying haplogroup M7a is attenuated in comparison to men carrying haplogroup D. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Accumulated evidence suggests a weak positive relationship between psychosocial stress and body mass index (BMI), but little is known about stress coping strategies and BMI. Objective: We aimed to examine if perceived stress and coping strategies are related to BMI, with any of their mutual interactions on BMI. Methods: This cross-sectional study included 5,063 men and 6,982 women aged 40-69 years. A self-administered questionnaire ascertained perceived stress and 5 items of coping strategies (emotion expression, emotional support seeking, positive reappraisal, problem solving, and disengagement). Analyses were performed by gender with adjustment for age, socioeconomic status, and lifestyle factors. Results: No significant associations were detected between perceived stress and BMI in either men (Ptrend = 0.09) or women (Ptrend = 0.58). In men, however, ‘disengagement’ showed an inverse association with BMI (Ptrend < 0.001), and ‘positive reappraisal’ and ‘problem solving’ revealed a positive association with BMI (Ptrend = 0.04 and 0.007, respectively) even after controlling for perceived stress. A possible interaction between perceived stress and ‘disengagement’ on BMI was found in men (Pinteraction = 0.027); the inverse association between ‘disengagement’ and BMI was more evident in higher levels of stress (β = −0.13, Ptrend = 0.21 in low; β = −0.22, Ptrend = 0.01 in medium; and β = −0.24, Ptrend = 0.06 in high). In men, ‘disengagement’ was inversely associated with overweight/obesity (odds ratio 0.79, 95% confidential interval 0.67-0.95), and “positive reappraisal” was positively associated with it (1.25, 1.02-1.54). Conclusions: Coping strategies may have an important role in developing overweight/obesity, particularly in men. [ABSTRACT FROM AUTHOR]

Background: Perceived stress and coping strategies may influence the risk of cardiovascular disease through their possible association with inflammation, but data remain controversial for perceived stress or scanty for coping strategies. Purpose: We examined the associations of perceived stress and coping strategies with serum high-sensitivity C-reactive protein (CRP) in a Japanese general population. Methods: This cross-sectional study included 2,971 men and 4,902 women aged 40-69 years who were enrolled between 2005 and 2007. Subjects with possible inflammation-related disease, CRP levels ≥3,000 ng/mL, or currently used analgesics or lipid-lowering drugs were excluded. Analyses were performed by gender with adjustment for lifestyle, socioeconomic, and psychosocial factors. Results: Unexpectedly, elevated perceived stress was significantly associated with lower CRP levels in men ( P < 0.001) but not in women ( P = 0.90) after adjustment for age and covariates. Among five items of coping strategies evaluated, 'disengagement' showed a significant inverse association with CRP in men only ( P = 0.027). In addition, a possible interaction between 'emotional support seeking' and perceived stress on CRP was detected in men ( P = 0.021); 'emotional support seeking' was associated with lower CRP at the high stress level only ( P = 0.028). Conclusions: Both perceived stress and coping strategies may be associated with systemic inflammation in Japanese men, yet caution must be exercised before accepting the stress-inflammation-disease pathway. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Timing of menopause affects postmenopausal health risks. The objective of this study was to evaluate the associations of the single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR)-related genes (PPARD, PPARG, and PPARGC1A) and environmental factors with timing of natural menopause among the general Japanese population. Study design: We analyzed cross-sectional data from 1758 women aged 40–69 years who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study. Main outcome measures: Associations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models. Results: Lower body mass index and later age at menarche were significantly associated with earlier natural menopause. Women with minor alleles at T-48444C in PPARD showed a significantly higher adjusted hazard ratio of 1.57 (95% confidence interval: 1.18–2.10) for earlier natural menopause. In contrast, women with minor alleles at Thr394Thr in PPARGC1A showed a significantly lower adjusted hazard ratio of 0.86 (0.76–0.97) for earlier natural menopause. These associations did not substantially alter when re-analyzed after excluding the subjects who self-reported a history of diabetes or the subjects whose age was more than 65 years. Conclusions: Gene variants in PPARD and PPARGC1A might be associated with timing of natural menopause, probably through direct actions on the ovaries, among the general Japanese population. [Copyright &y& Elsevier]

Background Secreted protein acidic and rich in cysteine (SPARC) may play a role in the prevention of colon cancer through exercise, while SPARC is considered as a promoter of insulin resistance. The purpose of the present study was to clarify the effects of replacing sedentary time with either light-intensity PA (LPA) or moderate- to vigorous-intensity PA (MVPA) on serum SPARC in a general population. Methods The study subjects were 4000 men and 6040 women (40 to 69 years) who participated in baseline surveys of a population-based cohort study. Sedentary time, LPA, and MVPA were objectively measured by an accelerometer. The serum SPARC concentration was measured by an enzyme-linked immunosorbent assay. Using an isotemporal substitution model, cross-sectional associations of replacing sedentary time with either LPA or MVPA on serum SPARC levels were analyzed according to sex. Adjustment was made for potential confounding factors. Results In men, replacing 60 min of sedentary time with 60 min of MVPA was associated with 23 ng/mL (confidence interval -43, -2) lower serum SPARC levels even after adjusting for confounders, including the BMI (P = 0.028), while no such association was observed for LPA. Furthermore, no such significant replacement effects were observed in women. Conclusions The current study showed that replacing sedentary time with MVPA results in reduced serum SPARC concentrations in men. Key messages Effect of habitual PA to decrease circulating SPARC is PA intensity-specific. [ABSTRACT FROM AUTHOR]