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健康超重/肥胖女性补充α-硫辛酸和/或二十碳五烯酸后尿液样本的非靶向代谢组学分析。

Untargeted metabolomic on urine samples after α-lipoic acid and/or eicosapentaenoic acid supplementation in healthy overweight/obese women.

机构信息

Centre for Nutrition Research, University of Navarra, Pamplona, Spain.

Department of Nutrition, Food Science, and Physiology, University of Navarra, Pamplona, Spain.

出版信息

Lipids Health Dis. 2018 May 9;17(1):103. doi: 10.1186/s12944-018-0750-4.

DOI:10.1186/s12944-018-0750-4
PMID:29743087
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5941619/
Abstract

BACKGROUND

Eicosapentaenoic acid (EPA) and α-lipoic acid (α-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS).

METHODS

This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), α-LA (0.3 g/d) and EPA+α-LA (1.3 g/d + 0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification.

RESULTS

Urine samples were scattered in the PCA scores plots in response to the supplementation with α-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the α-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with α-LA. This fact might be associated with antioxidant properties of both α-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and α-LA supplementation.

CONCLUSIONS

This metabolomic approach supports that the beneficial effects of α-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate.

TRIAL REGISTRATION

Clinicaltrials.gov NCT01138774 .

摘要

背景

二十碳五烯酸(EPA)和α-硫辛酸(α-LA)已被研究用于肥胖和心血管风险因素的有益影响。在当前的研究中,我们的目标是评估这两种脂质单独或联合在遵循能量限制饮食的健康超重/肥胖久坐女性中补充后代谢组学的变化。为此,我们使用液相色谱与飞行时间质谱联用(HPLC-TOF-MS)对尿液样本进行了非靶向代谢组学分析。

方法

这是一项为期 10 周的短期双盲安慰剂对照研究,采用平行营养设计。参与者被分配到以下 4 个实验组之一[对照组、EPA(1.3g/d)、α-LA(0.3g/d)和 EPA+α-LA(1.3g/d+0.3g/d)]。所有干预组均遵循能量限制饮食,比总能量消耗少 30%。分析了临床相关的生化测量值。在基线和 10 周后收集 24 小时尿液样本。对尿液样本进行非靶向代谢组学分析,进行主成分分析(PCA)和偏最小二乘判别分析(PLS-DA),以识别模式和特征代谢物。

结果

根据 α-LA 的给药情况,尿液样本在 PCA 评分图中分散。阳性电离中总共鉴定出 28 种可能的判别代谢物,负电离中有 6 种。值得注意的是,在补充 α-LA 的组中存在抗坏血酸中间代谢物(三羟基二氧己酸的异构体之一,或二羟基氧代己二酸盐)。这一事实可能与 α-LA 和抗坏血酸的抗氧化特性有关。表型参数与提供的假定代谢物之间的相关性提供了关于它们之间是否存在直接或间接关系的额外信息。特别有趣的是抗坏血酸中间代谢物与不对称二甲基精氨酸(ADMA)之间的负相关关系,以及超氧化物歧化酶(SOD)与 α-LA 补充之间的正相关关系。

结论

这种代谢组学方法支持 α-LA 给药对体重减轻的有益影响可能部分归因于三羟基二氧己酸的异构体介导的这种有机硫羧酸的抗氧化特性,或二羟基氧代己二酸盐。

试验注册

Clinicaltrials.gov NCT01138774。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc68/5941619/8d35b6b3daeb/12944_2018_750_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc68/5941619/8d35b6b3daeb/12944_2018_750_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc68/5941619/8d35b6b3daeb/12944_2018_750_Fig1_HTML.jpg

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