Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Abstract

Exosomal micro (mi)RNAs have been suggested to have important roles in abdominal obesity, and to be associated with metabolic alterations via posttranscriptional regulation of target genes. However, exosomal miRNA profiles in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have rarely been investigated. In the present study, microarray data were obtained from the Gene Expression Omnibus database with the following accession numbers: GSE68885 (exosomal miRNAs in SAT obtained from seven patients with obesity and five lean patients), GSE50574 (exosomal miRNAs in VAT obtained from seven patients with obesity and five lean patients) and GSE29718 [mRNAs in SAT (obtained from seven patients with obesity and eight lean patients) and VAT (obtained from three patients with obesity and two lean patients)]. Differentially expressed (DE)-miRNAs and differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2.0 database. Potential functions of DE-miRNA target genes were determined using the Database for Annotation, Visualization and Integrated Discovery. As a result, 10 exosomal DE-miRNAs were identified in SAT between patients with obesity and lean patients, while 58 DE-miRNAs were identified in VAT between patients with obesity and lean patients. miRNA (miR)-4517 was revealed to be a downregulated exosomal miRNA between SAT and VAT, while the other DE-miRNAs were SAT-(e.g. hsa-miR-3156-5p and hsa-miR-4460) or VAT-(e.g. hsa-miR-582-5p, hsa-miR-566 and miR-548) specific. Following overlapping with the target genes of DE-miRNAs, only one DEG [cluster of differentiation 86 (CD86)] was identified in SAT samples, whereas 25 DEGs (e.g. fibroblast growth factor 2 (FGF2), FOS like 2, AP-1 transcription factor subunit (FOSL2); and adenosine monophosphate deaminase 3 (AMPD3)] were identified in VAT samples. CD86 was revealed to be regulated by hsa-miR-3156-5p; whereas FGF2, FOSL2 and AMPD3 were revealed to be regulated by hsa-miR-582-5p, hsa-miR-566 and miR-548, respectively. Functional enrichment analysis demonstrated that these target genes may be associated with inflammation. In conclusion, exosomal miRNAs may represent underlying therapeutic targets for the treatment of abdominal obesity and metabolic disorders via regulation of inflammatory genes.

Epigenetic signatures underlying inflammation: an interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition

“…A bioinformatic approach identified a total of 23 active microRNAs (miRNAs) and transcription factor regulatory pathways significantly associated with obesity-related inflammation [87]. Also, a set of exosomal miRNAs differentially expressed in abdominal obesity was associated with inflammation [88]. Overweight and obesity led to deregulation of circulating inflammatory miRNAs, which may contribute to the heightened inflammatory state associated with these conditions [89].…”

MicroRNAs and their regulatory networks in Chinese Gushi chicken abdominal adipose tissue during postnatal late development

“…These studies have focused on the identification, expression, and function of miRNAs in adipose tissues of different anatomical depots [21–25], and these findings have helped to elucidate the molecular mechanisms underlying adipose tissue development in animals. However, previous studies were limited to humans, mice and a few agricultural animals, as well as metabolic diseases, such as obesity [26, 27].…”

Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs

“…The abundance of several adipocyte-derived exosomal miRNAs was altered in obese patients, and most of them were specific to the VAT or sWAT. Exosomal miRNAs derived from VAT were predicted to target mRNAs mainly involved in TGF-β and Wnt/β-catenin signaling [25,320]. Another study on circulating miRNAs in obese patients showed that miR-130b in serum was positively correlated with BMI (Figure 5).…”