Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine University of Oslo, Postboks 1046 Blindern, 0317 Oslo, Norway.
Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine University of Oslo, Postboks 1046 Blindern, 0317 Oslo, Norway.
Redox Biol. 2024 Jul;73:103192. doi: 10.1016/j.redox.2024.103192. Epub 2024 May 17.
In animals, dietary sulfur amino acid restriction (SAAR) improves metabolic health, possibly mediated by altering sulfur amino acid metabolism and enhanced anti-obesogenic processes in adipose tissue.
To assess the effects of SAAR over time on the plasma and urine SAA-related metabolites (sulfurome) in humans with overweight and obesity, and explore whether such changes were associated with body weight, body fat and adipose tissue gene expression.
Fifty-nine subjects were randomly allocated to SAAR (∼2 g SAA, n = 31) or a control diet (∼5.6 g SAA, n = 28) consisting of plant-based whole-foods and supplemented with capsules to titrate contents of SAA. Sulfurome metabolites in plasma and urine at baseline, 4 and 8 weeks were measured using HPLC and LC-MS/MS. mRNA-sequencing of subcutaneous white adipose tissue (scWAT) was performed to assess changes in gene expression. Data were analyzed with mixed model regression. Principal component analyses (PCA) were performed on the sulfurome data to identify potential signatures characterizing the response to SAAR.
SAAR led to marked decrease of the main urinary excretion product sulfate (p < 0.001) and plasma and/or 24-h urine concentrations of cystathionine, sulfite, thiosulfate, HS, hypotaurine and taurine. PCA revealed a distinct metabolic signature related to decreased transsulfuration and HS catabolism that predicted greater weight loss and android fat mass loss in SAAR vs. controls (all p < 0.05). This signature correlated positively with scWAT expression of genes in the tricarboxylic acid cycle, electron transport and β-oxidation (FDR = 0.02).
SAAR leads to distinct alterations of the plasma and urine sulfurome in humans, and predicted increased loss of weight and android fat mass, and adipose tissue lipolytic gene expression in scWAT. Our data suggest that SAA are linked to obesogenic processes and that SAAR may be useful for obesity and related disorders. TRIAL IDENTIFIER: https://clinicaltrials.gov/study/NCT04701346.
在动物中，饮食中硫氨基酸限制（SAAR）可改善代谢健康，这可能是通过改变硫氨基酸代谢和增强脂肪组织中的抗肥胖过程来介导的。
评估 SAAR 随时间对超重和肥胖人群的血浆和尿液中与硫氨基酸相关的代谢物（硫组）的影响，并探讨这些变化是否与体重、体脂肪和脂肪组织基因表达有关。
59 名受试者被随机分配到 SAAR（约 2gSAAR，n=31）或对照饮食（约 5.6gSAAR，n=28）组，饮食由植物性全食物组成，并补充胶囊以滴定 SAAR 的含量。使用 HPLC 和 LC-MS/MS 测量基线、4 周和 8 周时血浆和尿液中的硫组代谢物。对皮下白色脂肪组织（scWAT）进行 mRNA 测序，以评估基因表达的变化。数据采用混合模型回归进行分析。对硫组数据进行主成分分析（PCA），以确定反映 SAAR 反应的潜在特征。
SAAR 导致主要尿排泄产物硫酸盐显著减少（p<0.001），以及血浆和/或 24 小时尿中胱硫醚、亚硫酸盐、硫代硫酸盐、HS、次牛磺酸和牛磺酸的浓度降低。PCA 显示出与转硫作用和 HS 分解代谢减少相关的独特代谢特征，该特征预测 SAAR 比对照组体重减轻和男性型脂肪量减少更大（均 p<0.05）。该特征与 scWAT 中三羧酸循环、电子传递和β-氧化相关基因的表达呈正相关（FDR=0.02）。
SAAR 导致人类血浆和尿液硫组发生明显改变，并预测体重和男性型脂肪量以及 scWAT 中脂肪分解基因表达的增加。我们的数据表明，SAAR 与致肥胖过程有关，SAAR 可能对肥胖和相关疾病有用。
