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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.

SUBMITTER: Yang Z

PROVIDER: S-EPMC6102639 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Yang Zheng Z Wei Zhuying Z Wu Xia X Yang Huidi H

Molecular medicine reports 20180724 3

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 f ...[more]

PMID: 30066923

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Project description:BackgroundAdipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue-specific roles in systemic metabolic perturbations.ObjectiveWe sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications.MethodsPaired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found.ResultsOur analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways.ConclusionsOur work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues.

Dataset Information

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

Publications

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

Similar Datasets

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