Dietary restriction of methionine and cysteine is a well-described model that improves metabolic health in rodents. To investigate the translational potential in humans, we evaluated the effects of dietary methionine and cysteine restriction on cardiometabolic risk factors, plasma and urinary amino acid profile, serum fibroblast growth factor 21 (FGF21), and subcutaneous adipose tissue gene expression in women with overweight and obesity in a double-blind randomized controlled pilot study. Twenty women with overweight or obesity were allocated to a diet low (Met/Cys-low, n = 7), medium (Met/Cys-medium, n = 7) or high (Met/Cys-high, n = 6) in methionine and cysteine for 7 days. The diets differed only by methionine and cysteine content. Blood and urine were collected at day 0, 1, 3 and 7 and subcutaneous adipose tissue biopsies were taken at day 0 and 7. Plasma methionine and cystathionine and urinary total cysteine decreased, whereas FGF21 increased in the Met/Cys-low vs. Met/Cys-high group. The Met/Cys-low group had increased mRNA expression of lipogenic genes in adipose tissue including DGAT1. When we excluded one participant with high fasting insulin at baseline, the Met/Cys-low group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys-high group. The participants reported satisfactory compliance and that the diets were moderately easy to follow. Our data suggest that dietary methionine and cysteine restriction may have beneficial effects on circulating biomarkers, including FGF21, and influence subcutaneous adipose tissue gene expression. These results will aid in the design and implementation of future large-scale dietary interventions with methionine and cysteine restriction. Trial registration ClinicalTrials.gov Identifier: NCT03629392, registration date: 14/08/2018 https://clinicaltrials.gov/ct2/show/NCT03629392.

中文翻译：

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饮食蛋氨酸和半胱氨酸限制对超重或肥胖妇女血浆生物标志物，血清成纤维细胞生长因子21和脂肪组织基因表达的影响：一项双盲随机对照试验研究。

饮食中蛋氨酸和半胱氨酸的限制是一个众所周知的模型，可以改善啮齿动物的代谢健康。为了研究人类的翻译潜力，我们评估了饮食蛋氨酸和半胱氨酸限制对超重和肥胖妇女的心脏代谢危险因素，血浆和尿氨基酸谱，血清成纤维细胞生长因子21（FGF21）和皮下脂肪组织基因表达的影响。肥胖在双盲随机对照试验研究中。20名超重或肥胖的妇女在以下饮食中被分配为低饮食（Met / Cys-低，n = 7），中饮食（Met / Cys-中，n = 7）或高饮食（Met / Cys-高，n = 6）。蛋氨酸和半胱氨酸持续7天。饮食的区别仅在于蛋氨酸和半胱氨酸含量。在第0、1天收集血液和尿液 在Met / Cys-低组与Met / Cys-高组中，分别在第3天和第7天以及皮下脂肪组织活检进行了第0天和第7天的血浆甲硫氨酸和半胱氨酸和尿液总半胱氨酸减少，而FGF21增加。Met / Cys-low组在包括DGAT1的脂肪组织中增加了生脂基因的mRNA表达。当我们排除一名基线时空腹胰岛素高的参与者时，与Met / Cys高组相比，Met / Cys低组显示ACAC，DGAT1表达增加，FASN和SCD1表达增加。参与者报告满意的依从性，并且饮食适度容易遵循。我们的数据表明，饮食中蛋氨酸和半胱氨酸的限制可能对循环生物标志物（包括FGF21）产生有益影响，并影响皮下脂肪组织基因表达。这些结果将有助于设计和实施将来限制蛋氨酸和半胱氨酸的大规模饮食干预措施。试验注册ClinicalTrials.gov标识符：NCT03629392，注册日期：2018年8月14日https://clinicaltrials.gov/ct2/show/NCT03629392。