MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation.
MiRNA expression profile of human subcutaneous adipose and during adipocyte differentiation.
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DOI：
10.1371/journal.pone.0009022
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发表时间：
2010-02-02
期刊：
影响因子：
3.7
通讯作者：
Fernández-Real JM
中科院分区：
文献类型：
--
作者：
Ortega FJ;Moreno-Navarrete JM;Pardo G;Sabater M;Hummel M;Ferrer A;Rodriguez-Hermosa JI;Ruiz B;Ricart W;Peral B;Fernández-Real JM
脂肪生成的潜在调节因子包括微小RNA（miRNAs），最近已经显示与肥胖相关并且在脂肪库中差异表达的小的非编码RNA。然而，据我们所知，迄今为止还没有关于人脂肪形成过程中miRNA表达谱的研究。因此，本研究的目的是研究人类脂肪细胞和皮下脂肪组织中的miRNA模式是否与肥胖和合并症相关，以及脂肪细胞中的miRNA表达谱是否与脂肪生成相关。我们在分化过程中的人脂肪细胞和来自非肥胖（n = 6）和肥胖伴（n = 9）和不伴（n = 13）2型糖尿病（DM-2）女性的皮下脂肪样品中进行了723种人和76种病毒成熟miRNA的全球miRNA表达微阵列。 然后通过RT-PCR验证脂肪生成相关miRNA的变化。799个miRNAs中有50个（6.2%）在瘦和肥胖受试者的脂肪细胞之间存在显著差异。与前脂肪细胞相比，70种miRNAs（8.8%）在成熟脂肪细胞中高度且显著地上调或下调。另外，这799个miRNAs中的17个（2.1%）与人体测量（BMI）和/或代谢（空腹血糖和/或甘油三酯）参数相关。我们在有和没有DM-2的肥胖受试者的皮下脂肪中鉴定了11个显著失调的miRNAs（1.4%）。有趣的是，这些变化中的大多数与脂肪细胞分化过程中也显著失调的miRNAs相关。在人前脂肪细胞和成熟脂肪细胞中发现的显著的反向miRNA谱暗示了miRNA与脂肪形成之间的密切串扰。这些候选物可能代表肥胖和肥胖相关并发症的生物标志物和治疗靶点。
Potential regulators of adipogenesis include microRNAs (miRNAs), small non-coding RNAs that have been recently shown related to adiposity and differentially expressed in fat depots. However, to date no study is available, to our knowledge, regarding miRNAs expression profile during human adipogenesis. Thereby, the aim of this study was to investigate whether miRNA pattern in human fat cells and subcutaneous adipose tissue is associated to obesity and co-morbidities and whether miRNA expression profile in adipocytes is linked to adipogenesis. We performed a global miRNA expression microarray of 723 human and 76 viral mature miRNAs in human adipocytes during differentiation and in subcutaneous fat samples from non-obese (n = 6) and obese with (n = 9) and without (n = 13) Type-2 Diabetes Mellitus (DM-2) women. Changes in adipogenesis-related miRNAs were then validated by RT-PCR. Fifty of 799 miRNAs (6.2%) significantly differed between fat cells from lean and obese subjects. Seventy miRNAs (8.8%) were highly and significantly up or down-regulated in mature adipocytes as compared to pre-adipocytes. Otherwise, 17 of these 799 miRNAs (2.1%) were correlated with anthropometrical (BMI) and/or metabolic (fasting glucose and/or triglycerides) parameters. We identified 11 miRNAs (1.4%) significantly deregulated in subcutaneous fat from obese subjects with and without DM-2. Interestingly, most of these changes were associated with miRNAs also significantly deregulated during adipocyte differentiation. The remarkable inverse miRNA profile revealed for human pre-adipocytes and mature adipocytes hints at a closely crosstalk between miRNAs and adipogenesis. Such candidates may represent biomarkers and therapeutic targets for obesity and obesity-related complications.
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