Aims: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study ...aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites.Methods: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted.Results: NAFLD was positively associated with CAVI (coefficients 95% Confidence intervals (CI)=0.23 0.09–0.37; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI.Conclusions: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.
Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with ...smoking and HTP use in a large Japanese population to improve health risk assessment.Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.Conclusions: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.
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Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of ...plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys-at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.
Abstract only Background and Aim: To determine the protein intake associated with the prevalence of sarcopenia, we conducted a cross-sectional study of 1251 community-dwelling older Japanese aged 60 ...years and older. Methods: The mean age of the participants was 68.8 years, and the percentage of women was 56.7%. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 by low muscle mass (skeletal muscle mass), muscle strength (grip strength), and physical performance (gait speed). Protein and energy intake were assessed using a food frequency questionnaire (FFQ). Logistic regression models were used to estimate the multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) of the prevalence of sarcopenia according to gender-specific tertiles of protein intake as a percentage of total energy. Corresponding analyses were done also for protein intake per day and for protein intake per kg of body weight, separately, instead of protein intake as a percentage of total energy. Results: The prevalence of sarcopenia was 8.0% (100/1251). The median protein intake as a percentage of total energy, protein intake per day, and protein intake per body weight by gender were, in order, 11.8%E, 59.2 g/day, and 0.9 g/kg/day for males and 14.1%E, 54.7 g/day, and 1.0 g/kg/day for females. Since there was no gender interaction in the association between each protein intake and the prevalence of sarcopenia, we performed the analysis for males and females combined. The multivariable adjusted ORs (95%CI) of the prevalence of sarcopenia was lower in the high protein intake as a percentage of total energy (>12.6%E in males and >15.2%E in females, respectively) group (0.47 (0.27-0.83)) than in the low intake (<11.1%E in males and <13.4%E in females, respectively) group; the linear trend was significant (p =0.009). Similarly, we found a significantly inverse association for sarcopenia prevalence at protein intakes higher than 54.4 g/day for males and 50.6 g/day for females, compared to those with lower intakes. However, there was no association between protein intake per body weight and the prevalence of sarcopenia. We obtained similar results when the participants were restricted to those 65 years and older as a sensitivity analysis. Conclusion: Significant inverse associations were found between the prevalence of sarcopenia and protein intake in community-dwelling older Japanese. However, we should consider that protein intake assessed by the FFQ is often underestimated when discussing absolute protein intake for sarcopenia prevention.
Aims: Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study ...aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites. Methods: A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted. Results: NAFLD was positively associated with CAVI (coefficients 95% Confidence intervals (CI)=0.23 0.09-0.37; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI. Conclusions: NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.
The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision ...prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.
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The internal friction was measured for an Al-Cu-Fe icosahedral phase (i-phase) and an Al-Cu-Fe-Si 1/1 approximant phase (1/1-phase) by using a dynamical mechanical analyzer (DMA) in the frequency ...range 0.05-10 Hz and the temperature range 300-873 K. For the i-phase, four absorption peaks were observed at around 420, 580, 620 and 800 K, respectively. These were of the thermally activated relaxation type, and their activation parameters were evaluated. The parameters evaluated for the peak at 800 K indicate a relaxation process involving a collective atomic motion, which can be attributed to correlated phason jumps. This peak was absent for the 1/1-phase. These results are similar to the results of the internal friction measurements previously reported for an Al-Pd-Mn i-phase and its 1/1 approximant phase. Based on the phonon-phason dynamics model, the magnitudes of phason elastic constants were estimated for the Al-Cu-Fe i-phase.
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