Adipocyte-derived exosomal miRNAs: a novel mechanism for obesity-related disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03

AUTHORS

Sarah C. Ferrante, Evan P. Nadler, Dinesh K. Pillai, Monica J. Hubal, Zuyi Wang, Justin M. Wang, Heather Gordish-Dressman, Emily Koeck, Samantha Sevilla, Andrew A. Wiles, Robert J. Freishtat

ABSTRACT

BACKGROUND: Obesity is frequently complicated by comorbid conditions, yet how excess adipose contributes is poorly understood. Although adipocytes in obese individuals induce systemic inflammation via secreted cytokines, another potential mediator has recently been identified (i.e., adipocyte-derived exosomes). We hypothesized that adipocyte-derived exosomes contain mediators capable of activating end-organ inflammatory and fibrotic signaling pathways. METHODS: We developed techniques to quantify and characterize exosomes shed by adipocytes from seven obese (age: 12-17.5 y, BMI: 33-50 kg/m(2)) and five lean (age: 11-19 y, BMI: 22-25 kg/m(2)) subjects. RESULTS: Abundant exosomal miRNAs, but no mRNAs, were detected. Comparison of obese vs. lean visceral adipose donors detected 55 differentially expressed miRNAs (P < 0.05; fold change ≥|1.2|). qRT-PCR confirmed downregulation of miR-148b (ratio = 0.2 (95% confidence interval = 0.1, 0.6)) and miR-4269 (0.3 (0.1, 0.8)), and upregulation of miR-23b (6.2 (2.2, 17.8)) and miR-4429 (3.8 (1.1-13.4)). Pathways analysis identified TGF-β signaling and Wnt/β-catenin signaling among the top canonical pathways expected to be altered with visceral adiposity based on projected mRNA targets for the 55 differentially expressed miRNAs. A select mRNA target was validated in vitro. CONCLUSION: These data show that visceral adipocytes shed exosomal-mediators predicted to regulate key end-organ inflammatory and fibrotic signaling pathways. More... »

PAGES

447-454

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/pr.2014.202

DOI

http://dx.doi.org/10.1038/pr.2014.202

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017712312

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25518011


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