Battillo Daniel J, Malin Steven K
Department of Kinesiology and Health, Rutgers University, New Brunswick, New Jersey, USA.
Division of Endocrinology, Metabolism and Nutrition, Rutgers University, New Brunswick, New Jersey, USA.
Exp Physiol. 2025 Jul 20. doi: 10.1113/EP092550.
Trimethylamine N-oxide (TMAO) is linked to arterial stiffness and atherosclerosis. Cardiovascular disease (CVD) risk increases following menopause in women. Whether menopause influences plasma TMAO metabolism to mediate CVD risk is unknown. Women with obesity were classified as premenopausal (n = 13; 40.3 ± 2.7 years; 39.4 ± 2.0 kg/m) or postmenopausal (n = 22; 56.5 ± 1.1 years; 35.6 ± 0.9 kg/m) via self-reported presence/absence of menses (last 12 months). Men were age- and body mass index-matched to postmenopausal women (n = 16; 55.9 ± 2.1 years; 34.3 ± 1.2 kg/m) as controls to discern potential menopause-driven TMAO differences. Carotid-femoral pulse wave velocity (cfPWV) and pulse wave analysis (applanation tonometry) were analysed to assess arterial stiffness, aortic waveforms and blood pressure. Fasting plasma TMAO and precursors (carnitine, choline, betaine and trimethylamine (TMA)) were assessed (mass spectroscopy). A 180 min 75 g oral glucose tolerance test was performed to approximate insulin sensitivity and quantify vascular cell (vascular cell adhesion molecule 1 (VCAM-1)) and intercellular adhesion molecules (intercellular adhesion molecule 1 (ICAM-1)). Body composition (DXA/BodPod) and fitness ( ) were measured. Premenopausal women were younger than men and postmenopausal women (P < 0.0001, η = 2.29). Men had lower body fat (P = 0.001, η = 0.80) and higher fat-free mass (P = 0.004, η = 0.42) compared to both pre- and postmenopausal women. There were no differences among groups in fitness, insulin sensitivity, ICAM-1 or blood pressure (P > 0.05), but men had higher cfPWV (P = 0.040, η = 0.27) and VCAM-1 (P = 0.041, η = 0.32). Postmenopausal women had elevated TMAO (P = 0.040, η = 0.29), compared with men and premenopausal women, yet men had elevated TMA (P = 0.041, η = 0.17), carnitine (P = 0.003, η = 0.27), choline (P = 0.022, η = 0.35) and betaine (P < 0.0001, η = 0.59). Thus when taken together, menopause may raise TMAO in women, while older men appear to have unique TMAO precursor metabolism linked to CVD risk.
氧化三甲胺（TMAO）与动脉僵硬度和动脉粥样硬化有关。女性绝经后心血管疾病（CVD）风险增加。绝经是否会影响血浆TMAO代谢以介导CVD风险尚不清楚。通过自我报告的月经情况（过去12个月），将肥胖女性分为绝经前（n = 13；40.3±2.7岁；39.4±2.0kg/m²）或绝经后（n = 22；56.5±1.1岁；35.6±0.9kg/m²）。将男性按照年龄和体重指数与绝经后女性匹配（n = 16；55.9±2.1岁；34.3±1.2kg/m²）作为对照，以辨别潜在的绝经驱动的TMAO差异。分析颈动脉 - 股动脉脉搏波速度（cfPWV）和脉搏波分析（压平式眼压测量法）以评估动脉僵硬度、主动脉波形和血压。评估空腹血浆TMAO及其前体（肉碱、胆碱、甜菜碱和三甲胺（TMA））（质谱法）。进行180分钟75g口服葡萄糖耐量试验以评估胰岛素敏感性并量化血管细胞（血管细胞粘附分子1（VCAM - 1））和细胞间粘附分子（细胞间粘附分子1（ICAM -
1））。测量身体成分（双能X线吸收法/体脂仪）和健康状况（ ）。绝经前女性比男性和绝经后女性年轻（P < 0.0001，η = 2.29）。与绝经前和绝经后女性相比，男性体脂较低（P = 0.001，η = 0.80），去脂体重较高（P = 0.004，η = 0.42）。各组之间在健康状况、胰岛素敏感性、ICAM - 1或血压方面无差异（P > 0.05），但男性的cfPWV较高（P = 0.040，η = 0.27）和VCAM - 1较高（P = 0.041，η = 0.32）。与男性和绝经前女性相比，绝经后女性的TMAO升高（P = 0.040，η = 0.29），而男性的TMA升高（P = 0.041，η = 0.17）、肉碱升高（P = 0.003，η = 0.27）、胆碱升高（P = 0.022，η = 0.35）和甜菜碱升高（P < 0.0001，η = 0.59）。因此，综合来看，绝经可能会使女性的TMAO升高，而老年男性似乎具有与CVD风险相关的独特TMAO前体代谢。
