An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.

An Untargeted Metabolomics Approach to Characterize Short-Term and Long-Term Metabolic Changes after Bariatric Surgery.
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DOI:
10.1371/journal.pone.0161425
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Magnes C
Magnes C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Narath SH;Mautner SI;Svehlikova E;Schultes B;Pieber TR;Sinner FM;Gander E;Libiseller G;Schimek MG;Sourij H;Magnes C

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减肥手术是目前治疗肥胖最有效的方法之一,可以显著减轻体重,改善心血管危险因素,提高治疗患者的总体生存率。迄今为止,大多数研究都集中在减肥手术对代谢谱的短期影响上,并发现个体对手术的反应存在很大差异。本研究的目的是通过使用非靶向代谢组学来确定相关的代谢变化,不仅在减肥手术(Roux-en-Y胃旁路术)后不久,而且在干预后一年内。在两个研究中心(奥地利和瑞士)进行的前瞻性研究(NCT01271062)中,从44名患者手术前、出院后(手术后1-3周)和1年随访期间采集了132份血清样本。样本包括24例基线时患有2型糖尿病的患者,其中9例在一年后糖尿病缓解。采用液相色谱-高分辨质谱法(LC-HRMS, HILIC-QExactive)对样品进行分析。原始数据采用XCMS处理,并在质量控制的基础上通过分位数回归进行漂移校正。通过随机森林和单因素检验筛选出177个相关代谢特征,鉴定出36种代谢物。鉴定出的代谢物包括三甲胺- n -氧化物、丙氨酸、苯丙氨酸和硫酸吲哚基,这些都是已知的心血管风险标志物。此外,我们发现糖尿病缓解组与非缓解组相比,一年后丙氨酸显著降低。我们的分析强调了对接受减肥手术的受试者进行多个时间点评估的重要性,以确定治疗反应、心血管益处和糖尿病缓解的生物标志物。关键发现包括各种代谢物随时间变化的不同趋势模式,并证明短期变化不应该被用来确定减肥手术的重要长期影响。
Bariatric surgery is currently one of the most effective treatments for obesity and leads to significant weight reduction, improved cardiovascular risk factors and overall survival in treated patients. To date, most studies focused on short-term effects of bariatric surgery on the metabolic profile and found high variation in the individual responses to surgery. The aim of this study was to identify relevant metabolic changes not only shortly after bariatric surgery (Roux-en-Y gastric bypass) but also up to one year after the intervention by using untargeted metabolomics. 132 serum samples taken from 44 patients before surgery, after hospital discharge (1–3 weeks after surgery) and at a 1-year follow-up during a prospective study (NCT01271062) performed at two study centers (Austria and Switzerland). The samples included 24 patients with type 2 diabetes at baseline, thereof 9 with diabetes remission after one year. The samples were analyzed by using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS, HILIC-QExactive). Raw data was processed with XCMS and drift-corrected through quantile regression based on quality controls. 177 relevant metabolic features were selected through Random Forests and univariate testing and 36 metabolites were identified. Identified metabolites included trimethylamine-N-oxide, alanine, phenylalanine and indoxyl-sulfate which are known markers for cardiovascular risk. In addition we found a significant decrease in alanine after one year in the group of patients with diabetes remission relative to non-remission. Our analysis highlights the importance of assessing multiple points in time in subjects undergoing bariatric surgery to enable the identification of biomarkers for treatment response, cardiovascular benefit and diabetes remission. Key-findings include different trend pattern over time for various metabolites and demonstrated that short term changes should not necessarily be used to identify important long term effects of bariatric surgery.
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