Abstract
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®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, HbA1c, 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.
Highlights
MicroRNAs are small (21–25 nucleotides in length), non-coding RNAs, that play an important regulatory role in animals and plants by targeting mRNA transcripts for cleavage or translational repression [1,2,3]
The miRNA expression pattern was different in normal glucose tolerance (NGT) as compared to type 2 diabetes (T2D) patients (Table 2)
We found significantly higher expression of miR-17-5p, miR-132, miR-134 in omental fat of NGT compared to T2D, whereas the opposite pattern was found for miR-181a
Summary
MicroRNAs (miRNAs) are small (21–25 nucleotides in length), non-coding RNAs, that play an important regulatory role in animals and plants by targeting mRNA transcripts for cleavage or translational repression [1,2,3]. MiRNAs have been shown to modulate stem cell and adipocyte differentiation as well as insulin secretion [6,7,8]. Esau et al [9] found that reducing miRNA-143 by transfecting antisense oligonucleotides inhibits adipocyte differentiation in vitro, suggesting that miRNAs may play a role in the regulation of key adipose tissue processes and could represent novel targets for the treatment of obesity. MiRNAs have been shown to regulate metabolic processes, which are associated with type 2 diabetes including insulin signaling and glucose homeostasis [6,10]
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