Institut National de la Santé et de la Recherche Médicale, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases, 31432 Toulouse, France.
University of Toulouse, Paul Sabatier University, 31400 Toulouse, France.
J Clin Endocrinol Metab. 2017 Aug 1;102(8):2751-2761. doi: 10.1210/jc.2016-3997.
Although calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals.
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.
Individuals underwent 8 weeks of low-calorie diet, then 6 months of ad libitum diet.
Weight changes at the end of the DI.
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 β1 (TGF-β1) was responsible for downregulation of certain genes during DI in good controllers. Interestingly, ASPN is a TGF-β1 inhibitor.
We found circulating biomarkers associated with weight control that could influence weight management strategies and genes that may be prognostic for successful weight control.
尽管热量限制已被证明对减肥有益，但个体之间的长期体重控制效果存在差异。
鉴定饮食干预期间成功体重控制的生物标志物。
设计、设置和参与者：比较了 21 名肥胖个体在饮食干预期间体重减轻或体重增加的脂肪组织（AT）转录组。使用定量逆转录聚合酶链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，在来自同一研究的 310 名个体中对结果进行了验证。
个体接受 8 周低热量饮食，然后进行 6 个月的随意饮食。
DI 结束时的体重变化。
我们评估了在 DI 期间表达改变、编码分泌蛋白且以前未涉及体重控制的六个基因（EGFL6、FSTL3、CRYAB、TNMD、SPARC、IGFBP3），以及基线表达在体重控制良好和较差个体之间存在差异的基因（ASPN、USP53）。EGFL6、FSTL3 和 CRYAB 的血浆浓度变化与 AT 信使 RNA 表达一致；在体重控制良好的个体中，这些物质在 DI 期间均下降。ASP 及 USP53 在体重控制良好的个体中具有更高的基线表达。表达数量性状基因座分析发现与 AT 中 USP53 表达水平相关的多态性。确定了一个调控网络，其中转化生长因子β1（TGF-β1）负责在良好控制器的 DI 期间下调某些基因。有趣的是，ASP 是 TGF-β1 的抑制剂。
我们发现了与体重控制相关的循环生物标志物，这些标志物可能影响体重管理策略，以及可能对成功体重控制有预后作用的基因。
