Evidence from human, animal and cellular studies suggests that high plasma total cysteine (tCys) is causally linked to human obesity, but determinants of population tCys variability are unknown. We hypothesized that tCys elevation in obesity may be mediated by an altered tCys response to intake of its precursor, methionine. We investigated whether BMI influences the change in plasma tCys, total homocysteine (tHcy) and total cysteinylglycine (tCysGly) 6h following a 100 mg/kg oral methionine load in 800 healthy subjects and 750 cardiovascular disease (CVD) cases. Methionine loading decreased tCys from mean 275 (95% CI, 273, 277) μmol/L to 253 (251,255) μmol/L. The decline in tCys was less in overweight (−8%) and obese (−6%) compared to normal weight (−9%) subjects, adjusting for age, gender and CVD (P-_ANOVA = 0.006). Compared to normal weight subjects, individuals with obesity had a 2.8-fold likelihood (95% CI, 1.52, 5.01) of experiencing a rise (rather than decline), in tCys postload, after multiple adjustments. tCysGly also decreased postload, and the decline was similarly smaller in overweight (−18%) and obese (−15%) compared to normal weight (−21%) individuals (P-_ANOVA <0.001). The tHcy response was modified by CVD status, with an increase in tHcy postload being BMI-dependent in controls (P-_ANOVA <0.001) but not in CVD cases (P-_interaction = 0.07). Although the methionine dose used was supraphysiologic, these data suggest that an altered tCys response to ingested methionine occurs in obesity, whereby tCys might rise in response to dietary methionine. This may contribute to explaining why human obesity is consistently associated with elevated tCys.

来自人类，动物和细胞研究的证据表明，高血浆总半胱氨酸（tCys）与人类肥胖有因果关系，但人口tCys变异性的决定因素尚不清楚。我们假设肥胖中tCys升高可能是由对前体蛋氨酸摄入的tCys反应改变介导的。我们调查了800例健康受试者和750例心血管疾病（CVD）患者口服100 mg / kg甲硫氨酸后6h，BMI是否会影响血浆tCys，总同型半胱氨酸（tHcy）和总半胱氨酸（tCysGly）的变化。蛋氨酸负荷将tCys从平均值275（95％CI，273，277）μmol/ L降低到253（251,255）μmol/ L。在tCys的下降相比，正常体重（-9％）受试者少在超重（-8％）和肥胖（-6％），调整年龄，性别和CVD（P- _ANOVA = 0.006）。与正常体重的受试者相比，在多次调整后，肥胖患者的tCys后负荷上升（而不是下降）的可能性是2.8倍（95％CI，1.52，5.01）。tCysGly也降低了后负荷，与正常体重（−21％）的个体相比，超重（−18％）和肥胖（−15％）的下降幅度较小（P- _ANOVA <0.001）。tHcy反应因CVD状态而改变，对照组的tHcy后负荷增加是BMI依赖性的（P - _ANOVA <0.001），而在CVD情况下则不是（P-_相互作用 = 0.07）。尽管所用蛋氨酸的剂量是超生理学的，但这些数据表明，肥胖对tCys对摄入的蛋氨酸的反应发生了改变，从而对饮食蛋氨酸的tCys可能会升高。这可能有助于解释为什么人类肥胖与tCys升高始终相关。