Klöting Nora, Berthold Susan, Kovacs Peter, Schön Michael R, Fasshauer Mathias, Ruschke Karen, Stumvoll Michael, Blüher Matthias
Department of Medicine, University of Leipzig, Leipzig, Germany.
PLoS One. 2009;4(3):e4699. doi: 10.1371/journal.pone.0004699. Epub 2009 Mar 4.
MicroRNAs (miRNAs) are small non-coding RNAs, that play important regulatory roles in a variety of biological processes, including development, differentiation, apoptosis, and metabolism. In mammals, miRNAs have been shown to modulate adipocyte differentiation. Therefore, we performed a global miRNA gene expression assay in different fat depots of overweight and obese individuals to investigate whether miRNA expression in human adipose tissue is fat-depot specific and associated with parameters of obesity and glucose metabolism. Paired samples of abdominal subcutaneous (SC) and intraabdominal omental adipose tissue were obtained from fifteen individuals with either normal glucose tolerance (NGT, n = 9) or newly diagnosed type 2 diabetes (T2D, n = 6). Expression of 155 miRNAs was carried out using the TaqMan(R)MicroRNA Assays Human Panel Early Access Kit (Applied Biosystems, Darmstadt, Germany). We identified expression of 106 (68%) miRNAs in human omental and SC adipose tissue. There was no miRNA exclusively expressed in either fat depot, suggesting common developmental origin of both fat depots. Sixteen miRNAs (4 in NGT, 12 in T2D group) showed a significant fat depot specific expression pattern. We identified significant correlations between the expression of miRNA-17-5p, -132, -99a, -134, 181a, -145, -197 and both adipose tissue morphology and key metabolic parameters, including visceral fat area, HbA(1c), fasting plasma glucose, and circulating leptin, adiponectin, interleukin-6. In conclusion, microRNA expression differences may contribute to intrinsic differences between omental and subcutaneous adipose tissue. In addition, human adipose tissue miRNA expression correlates with adipocyte phenotype, parameters of obesity and glucose metabolism.
微小RNA(miRNA)是一类小的非编码RNA,在多种生物学过程中发挥重要的调节作用,包括发育、分化、凋亡和代谢。在哺乳动物中,miRNA已被证明可调节脂肪细胞分化。因此,我们对超重和肥胖个体的不同脂肪库进行了全基因组miRNA基因表达分析,以研究人类脂肪组织中的miRNA表达是否具有脂肪库特异性,以及是否与肥胖和葡萄糖代谢参数相关。从15名葡萄糖耐量正常(NGT,n = 9)或新诊断的2型糖尿病(T2D,n = 6)个体中获取配对的腹部皮下(SC)和腹内网膜脂肪组织样本。使用TaqMan® MicroRNA分析人类早期访问试剂盒(德国达姆施塔特应用生物系统公司)对155种miRNA进行表达分析。我们在人类网膜和SC脂肪组织中鉴定出106种(68%)miRNA的表达。没有miRNA仅在单一脂肪库中表达,这表明两个脂肪库具有共同的发育起源。16种miRNA(NGT组4种,T2D组12种)表现出显著的脂肪库特异性表达模式。我们发现miRNA-17-5p、-132、-99a、-134、181a、-145、-197的表达与脂肪组织形态和关键代谢参数之间存在显著相关性,这些参数包括内脏脂肪面积、糖化血红蛋白(HbA1c)、空腹血糖以及循环中的瘦素、脂联素、白细胞介素-6。总之,微小RNA表达差异可能导致网膜和皮下脂肪组织之间的内在差异。此外,人类脂肪组织miRNA表达与脂肪细胞表型、肥胖和葡萄糖代谢参数相关。