Abstract
MicroRNAs (miRNAs) have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism, adipocyte differentiation. To determine the role of adipogenic miRNAs in the adipocyte differentiation process, we used microarray technology to monitor miRNA levels in human adipose-derived mesenchymal stem cells (hMSCs-Ad), human stromal vascular cells (SVCs) and differentiated adipocytes. 79 miRNAs were found to be differentially expressed, most of which are located in obesity related chromosomal regions but have not been previously linked to adipocyte differentiation process. A systematic search was made for relevant studies in academic data bases, involving the Gene Expression Omnibus (GEO) ArrayExpress, Pubmed and Embase database. Eight studies on human adipocyte differentiation or obesity were included in the final analysis. After combining our microarray data with meta-analysis of published microarray data, we detected 42 differently expressed miRNAs (meta-signature miRNAs) in mature adipocytes compared to SVCs or hMSCs-Ad. Our study shows meta-signature miRNAs specific for adipogenesis, several of which are correlated with key gene targets demonstrating functional relationships to pathways in BMP signaling pathway, Cell differentiation, Wnt signaling, insulin receptor signaling pathway, MAPK signaling, Cell cycle and lipid metabolic process. Our study shows that the first evidence of hsa-let-7 family, hsa-miR-15a-5p, hsa-miR-27a-3p, hsa-miR-106b-5p, hsa-miR-148a-3p and hsa-miR-26b-5p got a great weight in adipogenesis. We concluded that meta-signature miRNAs involved in adipocyte differentiation and provided pathophysiological roles and novel insight into obesity and its related metabolic diseases.
Highlights
Obesity has become a major worldwide health problem associated with metabolic and cardiovascular disorders
A larger number of microRNAs (79 miRNAs, 45 up-regulated miRNAs and 34 down-regulated miRNAs) were significantly up- or down-regulated in mature adipocytes compared to stromal vascular cells (SVCs) and hMSCs-Ad (Figure1, Supplementary Table 1).Our data showed that differentially expressed miRNAs were overlapping either in mature adipocytes versus SVCs or in mature adipocytes versus hMSCs-Ad (Supplementary Table 1, P< 0.05)
We identified that miR-148a, miR-26b, miR-132, miR-365 and miR-1908 were highly expressed in mature adipocytes with over 5-fold compared to SVCs/hMSCsAd
Summary
Obesity has become a major worldwide health problem associated with metabolic and cardiovascular disorders. Obesity is a progressive and multifactorial pathology characterized by excessive expansion of white adipose tissue, which due to an increase in adipocyte hyperplasia and hypertrophy [1]. Since obesity-related hyperplasia and hypertrophy are often associated with various metabolic disorders, proper understanding of the molecular events regulating adipogenesis and lipid metabolism can provide valuable information for exploiting comprehensive and effective therapeutic strategies against obesity. MicroRNAs (miRNAs), small non-coding RNAs of 18–25 nucleotides in length, which were seen to control gene expression in virtually obesity or other metabolism syndrome, were abundantly investigated relating to proliferation and differentiation of adipogenesis. The involvement of miRNAs in obesity pathogenesis is well established, as they can www.impactjournals.com/oncotarget behave as pro-adipogenic or adipogenic suppressor genes depending on the cellular function of their targets [4]
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