Pascut Devis, Tamini Sofia, Bresolin Silvia, Giraudi Pablo, Basso Giuseppe, Minocci Alessandro, Tiribelli Claudio, Grugni Graziano, Sartorio Alessandro
Fondazione Italiana Fegato - ONLUS, Trieste, Italy.
Istituto Auxologico Italiano, IRCCS, Experimental Laboratory for Auxo-endocrinological Research, Milan and Piancavallo (VB), Italy.
Endocr Connect. 2018 Dec 1;7(12):1262-1274. doi: 10.1530/EC-18-0329.
Prader-Willi syndrome (PWS) represents the most common genetic-derived obesity disorder caused by the loss of expression of genes located on the paternal chromosome 15q11.2-q13. The PWS phenotype shows peculiar physical, endocrine and metabolic characteristics compared to those observed in non-syndromic essential obesity. Since miRNAs have now a well-established role in many molecular pathways, including regulatory networks related to obesity, this pilot study was aimed to characterize the expression of circulating miRNAs in PWS compared to essential obesity. The circulating miRNome of 10 PWS and 10 obese subjects, adequately matched for age, BMI and sex, was profiled throughout Genechip miRNA 4.0 microarray analysis. We identified 362 out of 2578 mature miRNAs to be expressed in serum of the studied population. The circulating miRNA signature significantly characterising the two populations include 34 differently expressed RNAs. Among them, miR-24-3p, miR-122 and miR-23a-3p highly differ between the two groups with a FC >10 in obese compared to PWS. In the obese subjects, miR-7107-5p, miR-6880-3p, miR-6793-3p and miR-4258 were associated to the presence of steatosis. A different signature of miRNAs significantly distinguished PWS with steatosis from PWS without steatosis, involving miR-619-5p, miR-4507, miR-4656, miR-7847-3p and miR-6782-5p. The miRNA target GO enrichment analysis showed the different pathway involved in these two different forms of obesity. Although the rarity of PWS actually represents a limitation to the availability of large series, the present study provides novel hints on the molecular pathogenesis of syndromic and non-syndromic obesity.
普拉德-威利综合征（PWS）是最常见的由父源染色体15q11.2-q13上基因表达缺失引起的遗传性肥胖症。与非综合征性原发性肥胖相比，PWS表型具有独特的身体、内分泌和代谢特征。由于微小RNA（miRNA）在许多分子途径中已确立了作用，包括与肥胖相关的调控网络，本初步研究旨在表征PWS与原发性肥胖相比循环miRNA的表达情况。通过基因芯片miRNA 4.0微阵列分析对10名PWS患者和10名肥胖受试者（年龄、BMI和性别充分匹配）的循环miRNome进行了分析。我们在研究人群的血清中鉴定出2578个成熟miRNA中的362个有表达。显著区分这两个人群的循环miRNA特征包括34种差异表达的RNA。其中，miR-24-3p、miR-122和miR-23a-3p在两组之间差异很大，肥胖组与PWS组相比的倍数变化（FC）>10。在肥胖受试者中，miR-7107-5p、miR-6880-3p、miR-6793-3p和miR-4258与脂肪变性的存在有关。一组不同的miRNA特征显著区分了有脂肪变性的PWS与无脂肪变性的PWS，涉及miR-619-5p、miR-4507、miR-4656、miR-7847-3p和miR-6782-5p。miRNA靶基因的基因本体（GO）富集分析显示这两种不同形式的肥胖涉及不同的途径。尽管PWS的罕见性实际上限制了大样本的可获得性，但本研究为综合征性和非综合征性肥胖的分子发病机制提供了新线索。
