Laboratory of Molecular Biology, Nutrition, and Biotechnology (Nutrigenomics), University of the Balearic Islands (UIB), Campus de la Carretera. Valldemossa Km 7.5, Palma de Mallorca 07122, Spain.
J Clin Endocrinol Metab. 2012 Apr;97(4):E648-52. doi: 10.1210/jc.2011-2209. Epub 2012 Jan 25.
IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants Project) is a European multicenter study on childhood obesity. One of its goals is to define early biomarkers of risk associated with obesity and its comorbid conditions.
We considered blood cells as a new potential source of transcriptional biomarkers for these metabolic disorders and examined whether blood cell mRNA levels of some selected genes (LEPR, INSR, CPT1A, SLC27A2, UCP2, FASN, and PPARα) were altered in overweight children and whether their expression levels could be defined as markers of the insulin-resistant or dyslipidemic state associated with overweight.
Blood samples were obtained from 306 normal-weight and overweight children, aged 2-9 yr, from eight different European countries. Whole-blood mRNA levels were assessed by quantitative RT-PCR.
LEPR, INSR, and CPT1A mRNA levels were higher in overweight compared with normal-weight children (the two latter only in males), whereas SLC27A2 mRNA levels were lower in overweight children. Significant associations were also found between expression levels of LEPR, INSR, CPT1A, SLC27A2, FASN, PPARα, and different parameters, including body mass index, homeostasis model assessment index, and plasma triglycerides and cholesterol levels. These associations showed that high expression levels of CPT1A, SLC27A2, INSR, FASN, or PPARα may be indicative of a lower risk for the insulin-resistant or dyslipidemic state associated with obesity, whereas low LEPR mRNA levels appear as a marker of high low-density lipoprotein cholesterol, independently of body mass index.
These findings point toward the possibility of using the expression levels of these genes in blood cells as markers of metabolic status and can potentially provide an early warning of a future disorder.
IDEFICS(儿童和婴儿饮食和生活方式诱导的健康影响识别和预防项目)是一项针对儿童肥胖的欧洲多中心研究。其目标之一是确定与肥胖及其合并症相关的风险的早期生物标志物。
我们将血细胞视为这些代谢紊乱的新的潜在转录生物标志物来源,并研究超重儿童的某些选定基因(LEPR、INSR、CPT1A、SLC27A2、UCP2、FASN 和 PPARα)的血细胞 mRNA 水平是否发生改变,以及它们的表达水平是否可以定义为与超重相关的胰岛素抵抗或血脂异常状态的标志物。
从八个不同的欧洲国家采集了 306 名 2-9 岁的正常体重和超重儿童的血液样本。通过定量 RT-PCR 评估全血 mRNA 水平。
与正常体重儿童相比,超重儿童的 LEPR、INSR 和 CPT1A mRNA 水平更高(后两者仅在男性中),而 SLC27A2 mRNA 水平更低。LEPR、INSR、CPT1A、SLC27A2、FASN、PPARα 的表达水平与体重指数、稳态模型评估指数以及血浆甘油三酯和胆固醇水平等不同参数之间也存在显著相关性。这些相关性表明,CPT1A、SLC27A2、INSR、FASN 或 PPARα 的高表达水平可能预示着与肥胖相关的胰岛素抵抗或血脂异常状态的风险较低,而 LEPR mRNA 水平较低则表明独立于体重指数的 LDL 胆固醇水平较高。
这些发现表明,血细胞中这些基因的表达水平可能作为代谢状态的标志物,并可能为未来的疾病提供早期预警。