Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Postboks 1046, Blindern, 0317, Oslo, Norway.
The Lipid Clinic, Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, OUS HF Aker Sykehus, Postboks 4959, Nydalen, 0424, Oslo, Norway.
J Transl Med. 2020 Mar 11;18(1):122. doi: 10.1186/s12967-020-02288-x.
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 n = 7), medium (Met/Cys n = 7) or high (Met/Cys 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 vs. Met/Cys group. The Met/Cys 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 group showed increased expression of ACAC, DGAT1, and tendencies for increased expression of FASN and SCD1 compared to the Met/Cys 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.
蛋氨酸和半胱氨酸的饮食限制是一种经过充分描述的模型，可以改善啮齿动物的代谢健康。为了研究其在人类中的转化潜力，我们在一项双盲随机对照试验中评估了饮食中蛋氨酸和半胱氨酸限制对超重和肥胖女性的心血管代谢风险因素、血浆和尿液氨基酸谱、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。
20 名超重或肥胖的女性被分配到蛋氨酸和半胱氨酸含量低（Met/Cys n = 7）、中（Met/Cys n = 7）或高（Met/Cys n = 6）的饮食中，为期 7 天。这些饮食仅在蛋氨酸和半胱氨酸含量上有所不同。在第 0、1、3 和 7 天采集血液和尿液，在第 0 和 7 天采集皮下脂肪组织活检。
与 Met/Cys 组相比，Met/Cys 组的血浆蛋氨酸和胱硫醚以及尿总半胱氨酸降低，而 FGF21 升高。Met/Cys 组脂肪组织中包括 DGAT1 在内的脂肪生成基因的 mRNA 表达增加。当我们排除一名基线空腹胰岛素水平较高的参与者后，与 Met/Cys 组相比，Met/Cys 组的 ACAC、DGAT1 的表达增加，FASN 和 SCD1 的表达有增加的趋势。参与者报告了良好的依从性，并且这些饮食相对容易遵循。
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未来具有蛋氨酸和半胱氨酸限制的大型饮食干预研究。
ClinicalTrials.gov 标识符：NCT03629392，注册日期：2018 年 8 月 14 日，https://clinicaltrials.gov/ct2/show/NCT03629392。
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