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Background: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. Methods: Data of 1964 participants (40–75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008–2014 was analyzed. Serum TMAO concentration was quantified by HPLC–MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. Results: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 – 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 – 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. Conclusion: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. Trial registration: NCT 03179657. [ABSTRACT FROM AUTHOR]

The role of circulatory proteomics in osteoporosis is unclear. Proteome‐wide profiling holds the potential to offer mechanistic insights into osteoporosis. Serum proteome with 413 proteins was profiled by liquid chromatography–tandem mass spectrometry (LC–MS/MS) at baseline, and the 2nd, and 3rd follow‐ups (7704 person‐tests) in the prospective Chinese cohorts with 9.8 follow‐up years: discovery cohort (n = 1785) and internal validation cohort (n = 1630). Bone mineral density (BMD) was measured using dual‐energy X‐ray absorptiometry (DXA) at follow‐ups 1 through 3 at lumbar spine (LS) and femoral neck (FN). We used the Light Gradient Boosting Machine (LightGBM) to identify the osteoporosis (OP)‐related proteomic features. The relationships between serum proteins and BMD in the two cohorts were estimated by linear mixed‐effects model (LMM). Meta‐analysis was then performed to explore the combined associations. We identified 53 proteins associated with osteoporosis using LightGBM, and a meta‐analysis showed that 22 of these proteins illuminated a significant correlation with BMD (p < 0.05). The most common proteins among them were PHLD, SAMP, PEDF, HPTR, APOA1, SHBG, CO6, A2MG, CBPN, RAIN APOD, and THBG. The identified proteins were used to generate the biological age (BA) of bone. Each 1 SD‐year increase in KDM‐Proage was associated with higher risk of LS‐OP (hazard ratio [HR], 1.25; 95% CI, 1.14–1.36, p = 4.96 × 10−06), and FN‐OP (HR, 1.13; 95% CI, 1.02–1.23, p = 9.71 × 10−03). The findings uncovered that the apolipoproteins, zymoproteins, complements, and binding proteins presented new mechanistic insights into osteoporosis. Serum proteomics could be a crucial indicator for evaluating bone aging. [ABSTRACT FROM AUTHOR]

Background Many studies have investigated the effects of soy isoflavones on weight control, but few have focused on the role of equol, a gut-derived metabolite of daidzein with greater bioavailability than other soy isoflavones. Objectives This study examined the association of equol production with obesity and explored the mediating roles of equol-related gut microbiota and microbial carnitine metabolites. Methods This 6.6-y prospective study included 2958 Chinese adults (2011 females and 947 males) aged 60.6 ± 6.0 y (mean ± SD) at baseline. Urinary equol and isoflavones were measured using HPLC–tandem MS. BMI, percentage fat mass (%FM), and serum triglycerides (TGs) were assessed every 3 y. Metagenomics sequencing and assessment of carnitine metabolites in feces were performed in a subsample of 897 participants. Results Urinary equol, but not daidzein and genistein, was independently and inversely associated with the obesity-related indicators of BMI, %FM, and a biomarker (TGs). Equol producers (EPs) had lower odds of adiposity conditions and a reduced risk of 6.6-y obesity progression than non-EPs among total participants. Gut microbial analyses indicated that EPs had higher microbiome species richness (P =  3.42 × 10−5) and significantly different β-diversity of gut microbiota compared with the non-EP group (P  = 0.001), with 20 of 162 species differing significantly. EPs (compared with non-EPs) had higher abundances of Alistipes senegalensis and Coprococcus catus but lower abundances of Ruminococcus gnavus (false discovery rate <0.05). Among the 7 determined fecal acylcarnitine metabolites, palmitoylcarnitine, oleylcarnitine 18:1, and stearylcarnitine were inversely associated with EPs but positively correlated with obesity conditions and progression. Path analyses indicated that the beneficial association between equol and obesity might be mediated by gut microbiota and decreased production of 3 acylcarnitines in feces. Conclusions This study suggests a beneficial association between equol and obesity, mediated by the gut microbiome and acylcarnitines, in adults. This trial was registered at clinicaltrials.gov as NCT03179657. [ABSTRACT FROM AUTHOR]

Background Many studies have examined associations between dietary isoflavones and atherosclerosis, but few used objective biomarkers. Objectives We examined the associations of isoflavone biomarkers (primary analyses) and equol production (secondary analyses) with the progression of carotid intima–media thickness (cIMT), and whether inflammation, systolic blood pressure (SBP), blood lipids, and sex hormone–binding globulin (SHBG) mediated these associations, in Chinese adults. Methods This 8.8-y prospective study included 2572 subjects (40–75 y old) from the GNHS (Guangzhou Nutrition and Health Study; 2008–2019). The concentrations of daidzein, genistein, and equol were assayed by an HPLC-tandem MS in serum (n  = 2572) at baseline and in urine (n  = 2220) at 3-y intervals. The cIMT of the common carotid artery (CCA) and bifurcation segment were measured by B-mode ultrasound every 3 y, and the progressions of cIMT (∆ cIMT) were estimated using the regression method. Results Multivariable linear mixed-effects models (LMEMs) and ANCOVA revealed that subjects with higher serum isoflavones tended to have lower increases of CCA-cIMT. The mean ± SEM differences in 8.8-y ∆ CCA-cIMT between extreme tertiles of serum isoflavones were −17.1 ± 8.4, −20.6 ± 8.3, and −23.3 ± 10.4 μm for daidzein, total isoflavone, and equol (P -trends < 0.05), respectively. LMEMs showed that the estimated yearly changes (95% CIs) (μm/y) in CCA-IMT were −2.0 (−3.8, −0.3), −1.9 (−3.6, −0.1), and −2.1 (−3.8, −0.3) in the highest (compared with the lowest) tertile of daidzein, genistein, and total isoflavones, respectively (P -interaction < 0.05). Path analyses indicated that the serum equol–atherosclerosis association was mediated by increased SHBG and decreased SBP. Similar beneficial associations were observed in the secondary analyses. Conclusions Serum isoflavones and equol exposure were associated with reduced cIMT progression, mediated by SHBG and SBP. [ABSTRACT FROM AUTHOR]