Molecular Biomarkers for Weight Control in Obese Individuals Subjected to a Multiphase Dietary Intervention
Molecular Biomarkers for Weight Control in Obese Individuals Subjected to a Multiphase Dietary Intervention
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DOI：
10.1210/jc.2016-3997
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发表时间：
2017-08-01
影响因子：
5.8
通讯作者：
Viguerie, Nathalie
中科院分区：
文献类型：
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作者：
Bolton, Jennifer;Montastier, Emilie;Viguerie, Nathalie
背景：虽然卡路里限制已被证明对减肥有益，但长期的体重控制因个体而异。目的：确定饮食干预(DI)期间成功控制体重的生物标志物。设计、环境和参与者：比较了21名肥胖个体的脂肪组织(AT)转录本，这些肥胖者在DI期间保持体重减轻或恢复体重。通过定量逆转录聚合酶链式反应和酶联免疫吸附试验测量潜在循环生物标志物的蛋白水平，对同一研究中的310人的结果进行了验证。干预：受试者接受了8周的低卡路里饮食，然后是6个月的随意饮食。结果：测量：在DI结束时体重变化。结果：我们评估了6个在DI期间改变表达的基因，编码分泌蛋白，以前没有与体重控制有关的基因(Fleg6，FSTL3，CryAB，TNMD，SPARC，IGFBP3)，以及体重控制良好和不好的基因(ASPN，USP53)。血浆中EGFL6、FSTL3和CryAB浓度的变化反映了AT信使RNA的表达；在体重控制良好的个体中，所有这些都在DI期间下降。ASPN和USP53在体重控制良好的个体中有更高的基线表达。表达数量性状基因座分析发现，AT患者中USP53基因表达水平存在多态现象。确定了一个调控网络，其中转化生长因子β1(TGF-β1)负责在良好控制者的DI过程中下调某些基因。有趣的是，ASPN是一种转化生长因子-β1抑制剂。结论：我们发现了与体重控制相关的循环生物标志物，它们可能影响体重管理策略和可能预测成功体重控制的基因。
Context: Although calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals.Objective: To identify biomarkers of successful weight control during a dietary intervention (DI).Design, Setting, and Participants: Adipose tissue (AT) transcriptomes were compared between 21 obese individuals who either maintained weight loss or regained weight during the DI. Results were validated on 310 individuals from the same study using quantitative reverse transcription polymerase chain reaction and protein levels of potential circulating biomarkers measured by enzyme-linked immunosorbent assay.Intervention: Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet.Outcome Measure: Weight changes at the end of the DI.Results: We evaluated six genes that had altered expression during DI, encode secreted proteins, and have not previously been implicated in weight control (EGFL6, FSTL3, CRYAB, TNMD, SPARC, IGFBP3), as well as genes for which baseline expression differed between those with good and poor weight control (ASPN, USP53). Changes in plasma concentrations of EGFL6, FSTL3, and CRYAB mirrored AT messenger RNA expression; all decreased during DI in individuals with good weight control. ASPN and USP53 had higher baseline expression in individuals who went on to have good weight control. Expression quantitative trait loci analysis found polymorphisms associated with expression levels of USP53 in AT. A regulatory network was identified in which transforming growth factor beta 1 (TGF-beta 1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-beta 1 inhibitor.Conclusions: We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.